Happening @ Michigan https://events.umich.edu/list/rss RSS Feed for Happening @ Michigan Events at the University of Michigan. RNA Seminar featuring: Hiroaki Suga, University of Tokyo (September 28, 2020 9:00am) https://events.umich.edu/event/75805 75805-19608020@events.umich.edu Event Begins: Monday, September 28, 2020 9:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_PBHPayAvR8WobaSf3z0AUA

ABSTRACT: Macrocyclic peptides possess a number of pharmacological characteristics distinct from other well-established therapeutic molecular classes, resulting in a versatile drug modality with a unique profile of advantages. Macrocyclic peptides are accessible by not only chemical synthesis but also ribosomal synthesis. Particularly, recent inventions of the genetic code reprogramming integrated with an in vitro display format, referred to as RaPID (Random non-standard Peptides Integrated Discovery) system, have enabled us to screen mass libraries (>1 trillion members) of non-standard peptides containing multiple non-proteinogenic amino acids, giving unique properties of peptides distinct from conventional peptides, e.g. greater proteolytic stability, higher affinity (low nM to sub nM dissociation constants similar to antibodies), and superior pharmacokinetics. The field is rapidly growing evidenced by increasing interests from industrial sectors, including small start-ups as well as mega-pharmas, toward drug development efforts on macrocyclic peptides, which has led to several de novo discovered peptides entering clinical trials. This lecture discusses the aforementioned screening technology involving the method of “genetic code reprogramming” powered by flexizymes, and several showcases of therapeutic potentials of macrocyclic peptides.

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Lecture / Discussion Sun, 20 Sep 2020 13:22:07 -0400 2020-09-28T09:00:00-04:00 2020-09-28T10:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Hiroaki Suga, University of Tokyo
DCMB / CCMB Weekly Virtual Seminar - Xiaotian Zhang, Ph.D. (September 30, 2020 4:00pm) https://events.umich.edu/event/77549 77549-19883820@events.umich.edu Event Begins: Wednesday, September 30, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: The human genome is organized into small compartments to allow for the proper gene expression regulation in the physiological process. With the advance of next-generation sequencing and imaging technologies, we can now investigate how the genome is folded into 3D space and how the 3D genomic organization regulates gene expression in development and disease. Currently, most of the studies are focusing on CTCF and cohesion complex which partner together to facilitate the formation of topological associated domains (TAD). The presenter will mainly discuss his recently published work on the DNA methylation -3D genomics cross-talk. Unpublished work on the 3D genomics in AML will be discussed as well.

Short bio: Xiaotian Zhang obtained his Ph.D. at Baylor College of Medicine with Dr. Margaret Goodell on the role of DNA methylation synergy in leukemia development. He was previously the Van Andel special postdoc fellow in Gerd Pfeifer lab working on the 3D genomics in normal hematopoietic stem cell and leukemia. He is now a Research track faculty (Research Investigator) in Pathology Department under Tomek Cierpicki working on the HOXA regulation in leukemia development. Xiaotian's research focuses on the epigenetic regulation of key pathogenic genes in leukemia, particularly on high order chromatin structure in disease. He published on Nature Genetics, Molecular Cell and Blood as the first author and corresponding authors.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Lecture / Discussion Tue, 22 Sep 2020 09:31:31 -0400 2020-09-30T16:00:00-04:00 2020-09-30T17:00:00-04:00 Off Campus Location DCMB Seminar Series Lecture / Discussion Xiaotian Zhang, Ph.D., Research Investigator in the Department of Pathology at the University of Michigan
RNA Seminar featuring: Chase Weidmann, Washington University School of Medicine in St. Louis (October 5, 2020 4:00pm) https://events.umich.edu/event/76147 76147-19665691@events.umich.edu Event Begins: Monday, October 5, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_y9HTFl5RSOSJTJ5qtlhVcw

Keywords: mRNA regulation, noncoding RNA, RNA Structure, RNP granules

Abstract:
Chase Weidmann, Ph.D. has contributed broadly to the field of RNA Biology during his career, studying mechanisms of codon bias during translation, post-transcriptional regulation of mRNAs by RNA-binding proteins, the folding of long non-coding RNAs, and how RNA-protein interaction networks contribute to the function and assembly of functional RNP particles. Chase developed a chemical probing strategy and next-gen sequencing technology, called RNP-MaP, that maps the location of and cooperation between multi-protein networks on RNAs in live cells. Going forward, Chase is interested in understanding how alterations in RNA-binding protein profiles, a cell’s “RBPome”, confer deleterious activities onto noncoding RNAs in human disease, especially in cancer. To further empower this work and his future research program, Chase is now generating and integrating protein mass spectrometry data into his RBPome projects.

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Lecture / Discussion Wed, 16 Sep 2020 09:01:52 -0400 2020-10-05T16:00:00-04:00 2020-10-05T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
DCMB / CCMB Weekly Seminar (October 7, 2020 4:00pm) https://events.umich.edu/event/78232 78232-19996937@events.umich.edu Event Begins: Wednesday, October 7, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: The chromosomes of the human genome are organized in three-dimensions by compartmentalizing the cell nucleus and different genomic loci also interact with each other. However, the principles underlying such nuclear genome organization and its functional impact remain poorly understood. In this talk, I will introduce some of our recent work in developing machine learning methods by utilizing whole-genome mapping data to study the higher-order genome organization. Our methods reveal the spatial localization of chromosome regions and exploit chromatin interactome patterns within the cell nucleus in different cellular conditions, across mammalian species, and also in single-cell resolution. We hope that these algorithms will provide new insights into the principles of nuclear spatial organization.

Bio: Jian Ma is an Associate Professor in the Computational Biology Department within the School of Computer Science at Carnegie Mellon University. He was previously on the faculty of the University of Illinois at Urbana-Champaign. His lab develops algorithms to study the structure and function of the human genome with a focus on nuclear organization, gene regulation, comparative genomics, and single cell biology. He received several awards, including an NSF CAREER award and a Guggenheim Fellowship. He is the Contact PI of a UM1 Center project in the NIH 4D Nucleome Program (Phase 2; 2020-2025). https://www.cs.cmu.edu/~jianma/

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Tue, 06 Oct 2020 12:47:39 -0400 2020-10-07T16:00:00-04:00 2020-10-07T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: Jason Devlin, Ph.D. (October 9, 2020 10:00am) https://events.umich.edu/event/76029 76029-19655356@events.umich.edu Event Begins: Friday, October 9, 2020 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Jason Devlin, Ph.D.
Research Fellow
Stockbridge Lab
University of Michigan

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Livestream / Virtual Wed, 26 Aug 2020 15:58:32 -0400 2020-10-09T10:00:00-04:00 2020-10-09T11:00:00-04:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
DCMB / CCMB Weekly Seminar (October 14, 2020 4:00pm) https://events.umich.edu/event/78234 78234-19996940@events.umich.edu Event Begins: Wednesday, October 14, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Gaussian processes provide flexible non-parametric models of data and we are using them to model temporal and spatial patterns in gene expression. Single-cell omics measurements are destructive and one cannot follow the high-dimensional dynamics of genes across time in one cell. Similarly, the spatial context of cells is often lost or only known with reduced resolution. Computational methods are widely used to infer pseudo-temporal orderings of cells or to infer spatial locations. We show how Gaussian processes (GPs) can be used to model temporal and spatial relationships between genes and cells in these datasets. As examples I will show how we use Bayesian GPLVMs with informative priors to infer pseudo-temporal orderings for single-cell time course data [1] and branching GPs to identify gene-specific bifurcation points across pseudotime [2]. Gene expression data are often summarized as counts and there may be many zero values in the data due to limited sequencing depth. We therefore recently extended these methods to use negative binomial or zero-inflated negative binomial likelihoods and we show that this can lead to much improved performance over standard Gaussian noise models when identifying spatially varying genes from spatial transcriptomics data [3].

[1] Ahmed, S., Rattray, M., & Boukouvalas, A. (2019). GrandPrix: scaling up the Bayesian GPLVM for single-cell data. Bioinformatics, 35(1), 47-54.

[2] Boukouvalas, A., Hensman, J., & Rattray, M. (2018). BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process. Genome biology, 19(1), 65.

[3] BinTayyash, N., Georgaka, S., John, S. T., Ahmed, S., Boukouvalas, A., Hensman, J., & Rattray, M. (2020). Non-parametric modelling of temporal and spatial counts data from RNA-seq experiments. Bioarxiv https://doi.org/10.1101/2020.07.29.227207

Short bio: Magnus Rattray is Professor of Computational and Systems Biology at the University of Manchester and Director of the Institute for Data Science & AI. He works on the development of methods for machine learning and Bayesian inference with applications to large-scale biological and medical datasets. He has a long-standing interest in longitudinal data analysis and a more recent interest in modelling single-cell, spatial omics and live cell imaging microscopy data. He is a Fellow of the ELLIS Health Programme and the Alan Turing Institute and his research is funded by a Wellcome Trust Investigator Award.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Tue, 06 Oct 2020 13:35:21 -0400 2020-10-14T16:00:00-04:00 2020-10-14T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Magnus Rattray, PhD (Professor of Computational and Systems Biology, University of Manchester)
NeuroNetwork for Emerging Therapies Mini Symposium Series: Climate Change, the Environment & Health (October 15, 2020 2:00pm) https://events.umich.edu/event/77387 77387-19846079@events.umich.edu Event Begins: Thursday, October 15, 2020 2:00pm
Location: Off Campus Location
Organized By: NeuroNetwork for Emerging Therapies

It is impossible to ignore the evidence of the past decade - wildfires have made air on the west coast incredibly hazardous and children have been poisoned by drinking water at crucial ages of development. The environment we have created for ourselves is a serious threat to our health.

Eva Feldman, MD, PhD, Director of the NeuroNetwork for Emerging Therapies, will moderate the 30-minute mini symposium that discusses both global and local impacts that the environment has on our health. Along with Dr. Feldman, presentations will be made by Jonathan Overpeck, PhD, Dean of the School for Environment and Sustainability, who will address climate change and environmental justice; Stuart Batterman, PhD, a professor from the U-M School of Public Health, who will discuss how contaminants in the air affect your health; and Stephen Goutman, MD, MS, director of the Pranger ALS Clinic, who will talk about the association between environmental pollution and ALS.

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Conference / Symposium Thu, 17 Sep 2020 17:26:08 -0400 2020-10-15T14:00:00-04:00 2020-10-15T14:30:00-04:00 Off Campus Location NeuroNetwork for Emerging Therapies Conference / Symposium Climate Change, the Environment & Health Mini Symposium
Paths to PhD: Preparing for Grad School in the Biosciences (October 16, 2020 4:00pm) https://events.umich.edu/event/78233 78233-19996939@events.umich.edu Event Begins: Friday, October 16, 2020 4:00pm
Location: Off Campus Location
Organized By: Futures in Research, Science, Teaching - FIRST

A Zoom panel on applying and preparing for grad school, doing thesis research, and any other questions you have.

Friday, October 16th, at 4pm.

RSVP here: https://docs.google.com/forms/d/e/1FAIpQLScFP0DQjoBVYNrPy22NTheI5cffX17N3OAaRVIrCK9YSz_00g/viewform?usp=sf_link

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Workshop / Seminar Tue, 06 Oct 2020 13:21:33 -0400 2020-10-16T16:00:00-04:00 2020-10-16T17:00:00-04:00 Off Campus Location Futures in Research, Science, Teaching - FIRST Workshop / Seminar FIRST Logo
RNA Seminar featuring: Gene Yeo, University of California, San Diego (October 19, 2020 4:00pm) https://events.umich.edu/event/75807 75807-19608023@events.umich.edu Event Begins: Monday, October 19, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_CcI2trSATJy47aGtwrzhew

Abstract: The life-cycle of RNA from transcription to translational regulation is mediated by a diverse (>2000) set of proteins called RNA binding proteins. My lab studies the many roles that RNA binding proteins have in affecting RNA expression, splicing, transport and translation. Through our studies on RNA processing, we have introduced therapeutic strategies to treat neurodegenerative and muscular diseases, built cellular models of neurodevelopmental and neurodegenerative diseases and developed experimental and computational tools that enable the community to probe RNA binding protein-RNA interactions at scale. I will discuss (1) our established and new technologies to identify RNA targets of human RBPs at scale, (2) systematic assays to assign molecular roles to RBPs and (2) functional screens to identify RBPs implicated in cancer / RNA granule formation.

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Lecture / Discussion Wed, 16 Sep 2020 09:57:16 -0400 2020-10-19T16:00:00-04:00 2020-10-19T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Gene Yeo, University of California, San Diego
DCMB / CCMB Weekly Seminar (October 21, 2020 4:00pm) https://events.umich.edu/event/78531 78531-20058232@events.umich.edu Event Begins: Wednesday, October 21, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract
Although machine learning applications are now pervasive to every industry, adoption into healthcare remains a challenging and arduous process. Barriers to implementation include clinician trust, algorithm credibility and actionability, promoting clinician literacy in machine learning methods, and mitigating unintended consequences.

In the high-risk operating room setting, anesthesiologists are recognized leaders in patient safety, and manage uncertainty through careful considerations of risk and benefit based upon a thorough understanding of disease processes and treatment mechanisms. In this talk, the speaker highlights how obstacles to implementation of machine-learning based healthcare applications can be mitigated, and how an understanding of such applications can be promoted among clinically-minded anesthesiologists who may not necessarily be expert data scientists.

Short Bio:
Dr. Mathis has research interests in improving perioperative care for patients with advanced cardiovascular disease, particularly for patients with heart failure. As part of the Multicenter Perioperative Outcomes Group (MPOG), an international consortium of perioperative databases for which U-M serves as the coordinating center, he serves as Associate Research Director and plays a lead role in integration of MPOG data with data from national cardiac and thoracic surgery registries. He also has interests in leveraging novel data science methods to understand patterns within highly granular intraoperative physiologic data, studying hemodynamic responses to surgical and anesthetic stimuli as a means for early detection of cardiovascular diseases such as heart failure.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Wed, 14 Oct 2020 11:43:15 -0400 2020-10-21T16:00:00-04:00 2020-10-21T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Image which promotes the content of Dr. Mathis' talk (https://jamanetwork.com/collections/5584/critical-care-medicine)
U-M Structure Seminar: Christina Howard (October 23, 2020 10:00am) https://events.umich.edu/event/76030 76030-19655358@events.umich.edu Event Begins: Friday, October 23, 2020 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Christina Howard
Graduate Student
Cierpicki Lab
University of MIchigan

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Livestream / Virtual Wed, 26 Aug 2020 15:57:21 -0400 2020-10-23T10:00:00-04:00 2020-10-23T11:00:00-04:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: Aleksandra Filipovska, University of Western Australia (October 26, 2020 9:00am) https://events.umich.edu/event/75809 75809-19608025@events.umich.edu Event Begins: Monday, October 26, 2020 9:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED:https://umich.zoom.us/webinar/register/WN_f8wC8rrJQzuhYzTEXoW69Q

ABSTRACT:Mitochondria produce more than 90% of the energy required by our bodies and thereby have a fundamental role in cell and energy metabolism. Mitochondria are composed of proteins encoded by both the nuclear and mitochondrial genomes and the coordinated expression of both genomes is essential for energy production. Impaired energy production leads to mitochondrial dysfunction that causes or contributes significantly to a variety of diseases including metabolic disorders and cardiovascular diseases. Mitochondrial dysfunction is caused by mutations in nuclear or mitochondrial genes that encode proteins or regulatory RNAs essential for mitochondrial biogenesis. How uncoordinated gene expression causes mitochondrial dysfunction and compromised energy production in heart and metabolic diseases is poorly understood, making it difficult to develop effective treatments. To unravel how mitochondrial function fails and to identify therapeutic targets it is necessary (i) to understand how gene expression is regulated between mitochondria and the nucleus and (ii) how this regulation is disrupted in disease. We have created new and unique models of metabolic and cardiovascular diseases caused by mutations or loss of nuclear encoded RNA-binding proteins (RBPs) that regulate mitochondrial RNA metabolism and protein synthesis. These new models have identified that energy dysfunction can differentially affect specific organs such as the heart or liver, or multiple organs leading to heart failure or metabolic diseases that can be devastating, such as mitochondrial diseases, or may be as common as insulin resistance and obesity. I will discuss the mechanisms behind these diverse pathologies caused by impaired gene expression and energy dysfunction in heart and metabolic disease.

KEYWORDS: mitochondria, RNA, ribosomes, translation

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Lecture / Discussion Tue, 20 Oct 2020 14:16:54 -0400 2020-10-26T09:00:00-04:00 2020-10-26T10:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
Special Joint Seminar - Hosted by DCMB, Department of Mathematics, and the Smale Institute (October 26, 2020 12:00pm) https://events.umich.edu/event/78673 78673-20099541@events.umich.edu Event Begins: Monday, October 26, 2020 12:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Dr. Leland Hartwell won the Nobel Prize in Physiology or Medicine in 2001 for the discoveries of key regulators of the cell cycle.

“We want our students to have an authentic experience of science. Nearly all science activities designed for schools require the students to demonstrate an established scientific principle by getting the right answer. Getting the “right” answer is not authentic science. Science is the exploration of the unknown – the answer cannot be known.“
- Leland Hartwell

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Livestream / Virtual Mon, 19 Oct 2020 13:04:27 -0400 2020-10-26T12:00:00-04:00 2020-10-26T13:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Dr. Leland Hartwell, Nobel Laureate
Grad School in the Biosciences - Before, During, and After PhD (October 26, 2020 3:00pm) https://events.umich.edu/event/78568 78568-20066104@events.umich.edu Event Begins: Monday, October 26, 2020 3:00pm
Location: Off Campus Location
Organized By: Futures in Research, Science, Teaching - FIRST

A Zoom panel from faculty on applying and preparing for grad school, doing thesis research, and finding careers post-degree.

Monday, October 26th, at 3pm.

RSVP here:
https://docs.google.com/forms/d/e/1FAIpQLSedKIRGEuiUSu8IA0jPFpEZY7j-lXaOc8Wp_Xv0OJ0VpAo8Rg/viewform?usp=sf_link

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Workshop / Seminar Thu, 15 Oct 2020 09:28:26 -0400 2020-10-26T15:00:00-04:00 2020-10-26T16:00:00-04:00 Off Campus Location Futures in Research, Science, Teaching - FIRST Workshop / Seminar FIRST Logo
DCMB / CCMB Seminar (October 28, 2020 4:00pm) https://events.umich.edu/event/78528 78528-20058229@events.umich.edu Event Begins: Wednesday, October 28, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Single-cell RNA sequencing (scRNA-seq) allows researchers to examine the transcriptome at the single-cell resolution and has been increasingly employed as technologies continue to advance. Due to technical and biological reasons unique to scRNA-seq data, clustering and batch effect correction are almost indispensable to ensure valid and powerful data analysis. Multiple methods have been proposed for these two important tasks. For clustering, we have found that different methods, including state-of-the-art methods such as Seurat, SC3, CIDR, SIMLR, t-SNE + k-means, yield varying results in terms of both the number of clusters and actual cluster assignments. We have developed ensemble methods, SAFE-clustering and SAME-clustering, that leverages hyper-graph partitioning algorithms and a mixture model-based approach respectively to produce more robust and accurate ensemble solution on top of clustering results from individual methods. For batch effect correction, we have developed methods based on supervised mutual nearest neighbor detection to harness the power of known cell type labels for certain single cells. We benchmarked all methods in various scRNA-seq datasets to demonstrate their utilities.

Short bio: Yun Li, PhD is an Associate professor of Genetics and Biostatistics at the University of North Carolina, Chapel Hill. Dr. Li is a statistical geneticist with extensive experiences with method development and application on genotype imputation (developer of MaCH and MaCH-admix), genetic studies of recently admixed population, design and analysis of sequencing-based studies, analyses of multi-omics data including mRNA expression, DNA methylation and chromatin three dimensional organization. Dr. Li has been playing an active role in genetic studies of complex human traits resulting many GWAS and meta-analysis publications, including >30 in Nature, Science, Cell, and Nature Genetics. Dr. Li has been leading multiple R01 projects on statistical method development for complex trait genetics. Dr. Li has also been the Director for the Data Science Core of IDDRC (Intellectual and Developmental Disabilities Research Center). Dr. Li has received many awards and became the Thomson Reuters Highly Cited Researcher due to her high impact scientific work. Specifically, her work has been cited >60,000 times with h-index of 64 and i10-index of 113.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Wed, 14 Oct 2020 10:41:20 -0400 2020-10-28T16:00:00-04:00 2020-10-28T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Yun Li, PhD (Associate Professor of Genetics & Biostatistics; Adjunct Associate Professor, Applied Physical Sciences at School of Medicine, Genetics at University of North Carolina)
DCMB / CCMB Weekly Seminar (November 4, 2020 4:00pm) https://events.umich.edu/event/78770 78770-20121164@events.umich.edu Event Begins: Wednesday, November 4, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Metabolomics is a powerful approach to characterize small molecules produced in cells, tissues, and other biological systems. Metabolites are direct products of enzymatic reactions and provide a snapshot of cellular activities. Metabolomics-based research has already had a profound impact on biomarker discovery, nutritional analysis, and other biomedical and biological discoveries. The most pressing problem in metabolomics however is identifying compounds in the sample-under-study from the metabolomics measurements. Current analysis tools are capable of annotating only a small portion of sample measurements.

In this talk, we present machine learning solutions to three challenges related to the interpretation of metabolomics data. To mimic the function of a mass spectrometer in generating a mass spectrum, we use graph neural networks to translate a molecular structure into its respective spectral signature. To interpret the biological measurements in the context of the biological sample, we use Bayesan learning to deduce the likelihood of pathway activities. To suggest putative candidate molecules that are biologically relevant matches to the measured spectra, we explore several methods for predicting possible enzymatic products. We discuss several results, highlighting the value of using machine learning for advancing metabolomics analysis.

Short bio: Soha Hassoun is Professor and Past Chair of the Department of Computer Science at Tufts University. Soha received her undergraduate degree in Electrical Engineering from South Dakota State University, the Master's degree from MIT, and the Ph.D. degree from the Department of Computer Science and Engineering, University of Washington in Seattle. Soha’s lab uses Machine Learning to develop analysis and discovery tools for synthetic and systems biology, with a focus on enzyme promiscuity prediction and metabolomics analysis. Soha was a recipient of the NSF CAREER Award, and several technical and service awards from various professional societies. She provided technical leadership for several conferences including ICCAD and DAC. She co-founded the International Workshop on Bio-Design Automation in 2009. Soha serves on the board of the Computing Research Association's Committee on Widening Participation in Computing Research.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Thu, 22 Oct 2020 11:33:23 -0400 2020-11-04T16:00:00-05:00 2020-11-04T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
Writing Graduate School Application Statements (November 6, 2020 3:00pm) https://events.umich.edu/event/78947 78947-20160622@events.umich.edu Event Begins: Friday, November 6, 2020 3:00pm
Location: Off Campus Location
Organized By: Futures in Research, Science, Teaching - FIRST

What to include/avoid and how to frame your story while writing academic and personal statements for research-based grad programs.

RSVP: https://forms.gle/No9TpCrotxxuPk1B8

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Workshop / Seminar Tue, 27 Oct 2020 11:39:48 -0400 2020-11-06T15:00:00-05:00 2020-11-06T16:00:00-05:00 Off Campus Location Futures in Research, Science, Teaching - FIRST Workshop / Seminar
DCMB / CCMB Weekly Seminar (November 11, 2020 4:00pm) https://events.umich.edu/event/79286 79286-20264787@events.umich.edu Event Begins: Wednesday, November 11, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: There is a growing understanding that stress and depression during the process of training to become physicians is high. In this talk, we will discuss how we have used mobile and wearable data as well as genomics to understand the prevalence in the US and China, drivers and possible solutions about training physician depression and how the COVID-19 pandemic has affected them in the two countries.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Mon, 09 Nov 2020 14:13:58 -0500 2020-11-11T16:00:00-05:00 2020-11-11T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Drs. Margit Burmeister and Srijan Sen
U-M Structure Seminar: Regulation of kinesin motor activity (November 13, 2020 10:00am) https://events.umich.edu/event/76031 76031-19655359@events.umich.edu Event Begins: Friday, November 13, 2020 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Zhenyu Tan
University of Michigan
Graduate Student
Cianfrocco Clab

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Livestream / Virtual Mon, 02 Nov 2020 08:33:15 -0500 2020-11-13T10:00:00-05:00 2020-11-13T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: Michelle Hastings, Professor, Rosalind Franklin University of Medicine and Science (November 16, 2020 4:00pm) https://events.umich.edu/event/75868 75868-19615934@events.umich.edu Event Begins: Monday, November 16, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

https://umich.zoom.us/webinar/register/WN_VWX5SY6lSiaNyh5Weh8cHw

Michelle L. Hastings, PhD
Professor, Cell Biology and Anatomy
Director, Center for Genetic Diseases
Rosalind Franklin University of Medicine and Science

ABSTRACT: Antisense oligonucleotides (ASOs) have proven to be an effective therapeutic platform for the treatment of disease. These short, single-stranded, modified nucleotides function by base-pairing with the complementary sequence of an RNA and modulating gene expression in a manner that is dependent on the ASO design and targeting site. We have used ASOs to normalize aberrant gene expression associated with a number of diseases of the nervous system including Alzheimer’s and Parkinson’s disease and Usher syndrome. One of our approaches is under development for the treatment of CLN3 Batten disease, a fatal, pediatric lysosomal storage disease caused by mutations in a gene encoding the lysosomal membrane protein CLN3. The most common mutation associated with CLN3 Batten is a deletion of exons 7 and 8 (CLN3Δex78), which disrupts the mRNA open reading frame by creating a premature termination codon that results in the production of a truncated protein. We devised a therapeutic strategy for treating CLN3 Batten Disease using an ASO that basepairs to CLN3 pre-mRNA and alters splicing to correct the open reading frame of the mutated transcript. Treatment of CLN3Δex78 neonatal mice by intracerebroventricular injection of the ASO resulted in the desired splicing effect throughout the central nervous system, improved motor deficits associated with the disease in mice, reduced histopathological features of the disease in the brain and extended life in a severe mouse model of the disease. Our results demonstrate that ASO-mediated reading frame correction is a promising therapeutic approach for CLN3 Batten disease.

KEYWORDS: pre-mRNA splicing, Antisense oligonucleotides, Usher syndrome, Batten Disease, lysosomal storage diseases

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Lecture / Discussion Wed, 07 Oct 2020 09:31:00 -0400 2020-11-16T16:00:00-05:00 2020-11-16T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
DCMB / CCMB Weekly Seminar (November 18, 2020 4:00pm) https://events.umich.edu/event/79290 79290-20264791@events.umich.edu Event Begins: Wednesday, November 18, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Genetic variation affecting gene expression is wide-spread within and among species. This variation reflects the combined actions of mutation introducing new genetic variants and selection eliminating deleterious ones. Comparative studies of gene expression in fruit flies, yeast, plants, and mice have shown that the relative contributions of cis- and trans-acting variants to expression differences change over evolutionary time, indicating that selection has different effects on cis- and trans-regulatory variants. To better understand the reasons for this now widely observed pattern, we have been systematically studying the effects of mutation and selection on expression of the TDH3 gene of the baker’s yeast Saccharomyces cerevisiae. This work has revealed differences between cis- and trans-regulatory mutations in their frequency, effects, and dominance. Differences in pleiotropy are also generally assumed to exist between cis- and trans-regulatory that affect their evolutionary fate, but have been difficult to measure. In this talk, I will discuss how newly arising cis- and trans-regulatory mutations affecting expression of this focal gene are structured within the regulatory network, their pleiotropic effects on expression of all other genes in the genome, and how these pleiotropic effects influence fitness. A computational model of regulatory evolution integrating empirically observed differences in properties of cis- and trans-regulatory mutations will also be presented and discussed.

Patricia Wittkopp received a BS from the University of Michigan, a PhD from the University of Wisconsin, and did postdoctoral work at Cornell University. In 2005, she began a faculty position at the University of Michigan, where she is now the Sally L. Allen Collegiate Professor and Arthur F Thurnau Professor in the Department of Ecology and Evolutionary Biology and the Department of Molecular, Cellular, and Developmental Biology, and is a member of the Center for Computational Medicine and Bioinformatics. Her research investigates the genetic basis of phenotypic evolution, with an emphasis on the evolution of gene expression. She was a Damon Runyon Cancer Research Fellow, an Alfred P Sloan Research Fellow, Guggenheim Fellow, and a recipient of a March of Dimes Starter Scholar Award, the Margaret Dayhoff Mid-Career Award from the Society of Molecular Biology and Evolution, and the Friedrich Wilhelm Bessel Research Award from the Alexander von Humboldt Foundation.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Mon, 09 Nov 2020 15:12:34 -0500 2020-11-18T16:00:00-05:00 2020-11-18T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
DCMB / CCMB Weekly Seminar (December 2, 2020 4:00pm) https://events.umich.edu/event/79631 79631-20436379@events.umich.edu Event Begins: Wednesday, December 2, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

ABSTRACT: The brain is made of networks of neurons that send information to each other via spikes. Sleep and wake are the most clearly definable brain states and each exerts unique effects upon neural network spiking activity. We used large-scale recordings in the frontal cortex of mice and rats to examine the activity of neurons during wake/sleep cycles and found that a novel form of homeostatic action is taken by sleep: homogenization of firing rates. Whereas it was previously believed that sleep simple decreased firing rates, we found that this was much more true of the most active neurons only, thereby reducing the variance of the population.

To extend this observation of homeostatic forced during sleep we also examine how sleep and wake states interact with learning and performance, which is also facilitated by sleep. We have therefore begun to record before, during and after learning sessions to determine how learning interacts with the usual homeostatic effects of sleep. Further we can also record how waking changes in brain states such as motivation and attention modulate firing and information processing by neurons during behavior itself.

Finally, our end-goal to translate these kinds of basic neurobiologic observations in healthy rodents to states of stress or treatments of stress. Unfortunately the chronic stress states of relevance to psychiatric disease do not last seconds but days and weeks. We have therefore begun to build new long-term recording environments to enable future experiments over these time-spans.

BIOGRAPHY:
Dr. Watson is an assistant professor in psychiatry at the University of Michigan. He grew up in Ann Arbor and then obtained his BA from Cornell University and his M.D. and Ph.D. degrees from Columbia University. During his Ph.D. he used two-photon microscopy to study the behavior of neurons in local cortical microcircuits. During his doctoral work he also participated in technical development of multi-beam two photon imaging techniques. Upon graduation from medical school, Dr. Watson pursued a residency in Psychiatry at Weill Cornell Medical College as well postdoctoral work at New York University. He received the National Institute for Mental Health’s Outstanding Resident Award, the American Psychiatric Association’s Lilly Research Fellowship and the Leon Levy Neuroscience Fellowship. He did a fellowship with Dr. Gyorgy Buzsaki at NYU to record ongoing activity in naturally behaving and sleeping animals wherein he showed that sleep reorganizes neuronal firing architecture in the neocortex in previously unknown ways. He is now combining his electrical recordings with behavioral tools to deepen his understanding of both use and regulation of cortical brain circuits.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Tue, 01 Dec 2020 09:45:44 -0500 2020-12-02T16:00:00-05:00 2020-12-02T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: Mobile loop dynamics in adenosyltransferase control binding and reactivity of coenzyme B12 (December 4, 2020 10:00am) https://events.umich.edu/event/76032 76032-19655360@events.umich.edu Event Begins: Friday, December 4, 2020 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Romila Mascarenhas, Ph.D.
Research Fellow
Banerjee Lab
University of Michigan

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Livestream / Virtual Mon, 02 Nov 2020 08:35:11 -0500 2020-12-04T10:00:00-05:00 2020-12-04T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: John Mattick, University of New South Wales, Sydney, Australia (December 7, 2020 5:00pm) https://events.umich.edu/event/75816 75816-19608031@events.umich.edu Event Begins: Monday, December 7, 2020 5:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_fCIiMkveTdq3D9-PKFLm6Q

ABSTRACT: The genomic programming of the development of complex organisms appears to have been misunderstood. The human genome contains just ~20,000 protein-coding genes, similar in number and with largely orthologous functions as those in other animals, including simple nematodes with only 1,000 somatic cells. By contrast, the extent of non-protein-coding DNA increases with increasing developmental complexity, reaching 98.8% in humans. Moreover, it is now clear that the majority of the genome is not junk but is differentially and dynamically transcribed to produce not only mRNAs but also tens if not hundreds of thousands of short and long non-protein-coding RNAs that show specific expression patterns and subcellular locations. Many of these noncoding RNAs have evolved rapidly under positive selection for adaptive radiation, and many have been shown to have important roles in development, brain function, cancer and other diseases. They function at many different levels of gene expression and cell biology, including translational control, formation of subcellular (phase-separated) domains, and guidance of the epigenetic processes and chromatin dynamics that underpin development, brain function and physiological adaptation, with plasticity enabled by RNA editing, RNA modification and retrotransposon mobilization. These discoveries mean that the assumption that combinatorial control by transcription factors and other regulatory proteins is sufficient to account for human ontogeny is incorrect, as are the circular assumptions about the neutral evolution of the genome. The challenge now is to determine the structure-function relationships of these RNAs and their mechanisms of action, as well as their place in the decisional hierarchies that control human development, physiology, learning and susceptibility to disorders.

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Lecture / Discussion Tue, 03 Nov 2020 16:51:46 -0500 2020-12-07T17:00:00-05:00 2020-12-07T18:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
Department of Computational Medicine & Bioinformatics Weekly Wednesday Seminar (December 9, 2020 4:00pm) https://events.umich.edu/event/79756 79756-20484062@events.umich.edu Event Begins: Wednesday, December 9, 2020 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Learning objectives:

1. Discuss the conceptual distinction and clinical utility of self-reported race/ethnicity and genetic ancestry in childhood asthma.
2. Discuss the role of genetic ancestry and socio-environmental exposures in childhood asthma.
3. Discuss ancestry-specific polygenic risk scores, precision medicine and childhood asthma disparities.

Short bio: Dr. Mersha is currently an Associate Professor in the Division of Asthma Research and leads the Population Genetics, Ancestry, and Bioinformatics (pGAB) Laboratory (https://research.cchmc.org/mershalab/Home.php).
Dr. Mersha’s research combines quantitative, ancestry and statistical genomics to unravel genetic and non-genetic contributions to complex diseases and racial disparities in human populations, particularly asthma and asthma-related allergic disorders. Much of his research is at the interface of genetic ancestry, statistics, bioinformatics, and functional genomics, and he is interested in cross-line disciplines to unravel the interplay between genome and envirome underlying asthma risk. His long-term research goal is to understand and dissect how biologic predisposition and environmental exposures interact to shape racial disparities in complex disorders.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Mon, 07 Dec 2020 11:27:42 -0500 2020-12-09T16:00:00-05:00 2020-12-09T17:15:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Tesfaye ("Tes") Mersha, PhD (Associate Professor, Division of Asthma Research at Cincinnati Children's Hospital Medical Center)
RNA Seminar featuring: Narry Kim, Seoul National University (December 14, 2020 4:00pm) https://events.umich.edu/event/75818 75818-19608034@events.umich.edu Event Begins: Monday, December 14, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_c9BFJM9dRGKn1WFF4L_wLg

ABSTRACT: Viruses rely heavily on RNA binding proteins for their success as pathogens. In this presentation, I will first talk about RNA tail modification which impacts viral and cellular gene expression. We found that TENT4 enzymes extend poly(A) tail of mRNAs with ‘mixed tails’ to delay deadenylation and stabilize the RNAs. Hepatitis B virus and human cytomegalovirus hijack this mechanism to efficiently stabilize their own RNAs. In the later part of my presentation, I will discuss our recent work on SARS-CoV-2. To delineate the viral transcriptomic architecture and provide a high-resolution map of SARS-CoV-2, we performed deep sequencing of infected cells. Our data define the canonical transcripts and noncanonical transcripts encoding unknown ORFs. More recently, we have also performed proteomic analyses of the SARS-CoV-2 ribonucleoprotein complex. We identify many proteins that directly interact with viral RNAs and modulate viral growth. Functional investigation of the viral transcripts and host proteins discovered in this study will open new directions to the research efforts to elucidate the life cycle and pathogenicity of SARS-CoV-2.

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Lecture / Discussion Wed, 02 Dec 2020 12:55:41 -0500 2020-12-14T16:00:00-05:00 2020-12-14T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Narry Kim, Seoul National University
U-M Structure Seminar: "Substrate Selectivity in Flavin-dependent Hydroxylases: From Evolutionary Pathways to Electronic Structure" (January 15, 2021 10:00am) https://events.umich.edu/event/76181 76181-19671614@events.umich.edu Event Begins: Friday, January 15, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Troy Wymore, Ph.D.
Assistant Research Scientist & Lecturer
University of Michigan

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Livestream / Virtual Thu, 10 Dec 2020 10:06:45 -0500 2021-01-15T10:00:00-05:00 2021-01-15T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
Department of Computational Medicine & Bioinformatics Seminar (January 27, 2021 4:00pm) https://events.umich.edu/event/80722 80722-20777538@events.umich.edu Event Begins: Wednesday, January 27, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Massively parallel single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) has opened the way to systematic tissue atlases in health and disease, but as the scale of data generation is growing, so is the need for computational pipelines for scaled analysis. We developed Cumulus, the first comprehensive cloud-based framework, to address the big data challenge arising from sc/snRNA-seq analysis. Cumulus combines the power of cloud computing with improvements in algorithm and implementation to achieve high scalability, low cost, user-friendliness and integrated support for a comprehensive set of features. We benchmark Cumulus on the Human Cell Atlas Census of Immune Cells dataset of bone marrow cells and show that it substantially improves efficiency over conventional frameworks, while maintaining or improving the quality of results, enabling large-scale studies.

In recent years, biologists have found that sc/snRNA-seq alone is not enough to reveal the full picture of how cells function and coordinate with each other in a complex tissue. They begin to couple sc/snRNA-seq with other common data modalities, such as single-cell ATAC-seq (scATAC-seq), single-cell Immune Repertoire sequencing (scIR-seq), spatial transcriptomics and mass cytometry. This data coupling is called single-cell multimodal omics. As it is becoming a new common practice, new analysis needs emerge along with two major computational challenges: big data challenge and integration challenge. The big data challenge requires us to develop scalable computational infrastructure and algorithms to deal with the ever-growing large datasets produced from the community. The integration challenge requires us to design new algorithms to enable holistic integration of heterogeneous data from different modalities. In the last part of my talk, I will discuss my team’s efforts and plans to develop Cumulus as an integrated data analysis framework for scaled single-cell multimodal omics.

Single-cell multimodal omics has the potential to provide a more comprehensive characterization of complex multicellular systems than the sum of its parts. As the datasets produced from the community keep growing substantially, the enhanced Cumulus will continue playing an important role in the effort to build atlases of complex tissues and organs at higher cellular resolution, and in leveraging them to understand the human body in health and disease.

Short bio: Dr. Bo Li is an assistant professor of medicine at Harvard Medical School, the director of Bioinformatics and Computational Biology at Center for Immunology Inflammatory Diseases, Massachusetts General Hospital, and an associate member of the Broad Institute of MIT and Harvard. His research focuses on large-scale single-cell and single-nucleus genomics data analysis. He received his Ph.D. in computer science from UW-Madison and completed two postdoctoral trainings with Dr. Lior Pachter at UC Berkeley and Dr. Aviv Regev at Broad Institute. He is best known for developing RSEM, an impactful RNA-seq transcript quantification software. RSEM is cited 9,384 times (Google Scholar) and adopted by several big consortia such as TCGA, ENCODE, GTEx and TOPMed.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Wed, 13 Jan 2021 14:32:34 -0500 2021-01-27T16:00:00-05:00 2021-01-27T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Bo Li, PhD (Assistant Professor at Harvard Medical School in Boston, MA)
RNA Seminar featuring: Jeff Twiss, MD, PhD, SmartState Chair in Childhood Neurotherapeutics, Professor of Biological Sciences, University of South Carolina (February 1, 2021 4:00pm) https://events.umich.edu/event/75813 75813-19608028@events.umich.edu Event Begins: Monday, February 1, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_Rss4i-7WTwyf8m8ogCPXEQ

Abstract: Neurons are extremely polarized cells with axonal and dendritic processes extending 100 to 1000 fold longer or more than the cell body diameter. Our lab has been interested in how axons grow to such great distances and how they respond to injury. mRNAs are transported into axons, with their localized translation providing the axon with autonomy to respond to different stimuli by modifying their local proteome. Transport, translation, and stability of axonal mRNAs is driven by interactions with RNA binding proteins and different signaling cascades. I will focus on recent work that gives insight into how specificity of these mechanisms is driven for different cohorts of axonal mRNAs.

Keywords - Neuron, Axon, RNA transport, Translational regulation

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Lecture / Discussion Fri, 15 Jan 2021 14:13:00 -0500 2021-02-01T16:00:00-05:00 2021-02-01T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Jeff Twiss, University of South Carolina
CCMB / DCMB Weekly Seminar Series (February 3, 2021 4:00pm) https://events.umich.edu/event/81571 81571-20927558@events.umich.edu Event Begins: Wednesday, February 3, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:
Understanding intra-tumour heterogeneity (ITH), in particular identifying the presence of subclonal populations of cancer cells that may respond differently to treatments, is key to support precision medicine approaches. Capturing ITH from genomic measures raises however a number of computational challenges. In this talk I will present CloneSig, a method to infer ITH from "bulk" genomic data, in particular whole-exome sequencing data, and capture changes in mutational processes active in different subclones. I will then discuss the promises of single-cell genomics and some challenges it raises, in particular to transform raw count data into useful representations, integrate heterogeneous modalities, and learn gene regulation.

Short bio: Jean-Philippe Vert has been a research scientist at Google Brain in Paris and adjunct researcher at PSL University Mines ParisTech since 2018. He graduated from Ecole Polytechnique and holds a PhD in mathematics from Paris University. He was research professor and the founding director of the Centre for Computational Biology at Mines ParisTech from 2006 to 2018, team leader at the Curie Institute on computational biology of cancer (2008-2018), visiting scholar at UC Berkeley (2015-2016), and professor at the department of mathematics of Ecole normale supérieure in Paris (2016-2018).
His research interest concerns the development of statistical and machine learning methods, particularly to model complex, high-dimensional and structured data, with an application focus on computational biology, genomics and precision medicine. His recent contributions include new methods to embed structured data such as strings, graphs or permutations to vector spaces, regularization techniques to learn from limited amounts of data, and computationally efficient techniques for pattern detection and feature selection.
He is also working on several medical applications in cancer research, including quantifying and modeling cancer heterogeneity, predicting response to therapy, and modeling the genome and epigenome of cancer cells at the single-cell level.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Mon, 01 Feb 2021 14:12:04 -0500 2021-02-03T16:00:00-05:00 2021-02-03T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Jean-Philippe Vert, PhD (Research Scientist at Google Brain in Paris, Adjunct Researcher at PSL University Mines ParisTech)
CCMB / DCMB Weekly Seminar (February 10, 2021 4:00pm) https://events.umich.edu/event/81413 81413-20893777@events.umich.edu Event Begins: Wednesday, February 10, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: The increasing omics data and advanced AI technology present a great opportunity for novel biomarker-driven cancer therapies. My talk will cover two parts. First, I will introduce DrBioRight, a natural language-oriented and AI-driven analytic platform for omic data analysis. This platform allows users to perform analysis directly through human languages and it improves the performance through adaptive learning. Armed with NLP and AI technologies, this analytic will maximize the utility of omics data and lead to a new paradigm for biomedical research. Second, I will discuss our recent work on enhancer RNAs. We show that the eRNAs provide explanatory power for cancer phenotypes beyond that provided by mRNA expression through resolving intratumoral heterogeneity with enhancer cell-type specificity. Our study provides a high-resolution map of eRNA loci through which enhancer activities can be quantified by RNA-seq, enabling a broad range of biomedical investigations.

Bio: Dr. Liang is a Barnhart Family Distinguished Professor in Targeted Therapies and the Deputy Chair of Department of Bioinformatics and Computational Biology at the University of Texas MD Anderson Cancer Center. He is also a professor in the Department of Systems Biology. He received his B.S. in chemistry from Peking University (China) in 2001 and Ph.D. in quantitative and computational biology from Princeton University (NJ, USA) in 2006. Dr. Liang then finished his postdoctoral training in evolutionary and computational genomics at the University of Chicago. He joined MD Anderson Cancer Center as Assistant Professor and started his own group in 2009.
At MD Anderson, Dr. Liang’s group focuses on bioinformatics tool development, integrated cancer genomic analysis, regulatory RNA regulation/modification, and cancer systems biology. His systematic studies on enhancer regulation, RNA editing, functional proteomics, sex effects, and driver mutations in cancer have generated profound impacts on the biomedical research community and attracted wide attention such as The Wall Street Journal and Newsweek. The bioinformatics tools his group developed (such as TCPA, TANRIC, FASMIC, DrBioRight) collectively have >110,000 active users worldwide. Since 2010, he has published >140 papers total citation >25,000 times), including 41 corresponding-author papers in top journals such as Cell, Cancer Cell, Nature Genetics, Nature Biotechnology, and Nature Methods.
Dr. Liang has taken leadership roles in large cancer consortium projects, including chair of The Cancer Genome Atlas (TCGA) PanCanAtlas working groups, one co-leader of International Cancer Genome Consortium (ICGC) Pan-Cancer Whole Genome Analysis Project, and one co-chair of NCI Genomic Data Commons (GDC) QC working group. He won several awards including MD Anderson R. Lee Clark Fellow Award (2014), the University of Texas System STARS Award (2015), MD Anderson Faculty Scholar Award (2018), and AACR Team Science Award (2020). He is an elected Fellow of American Association for the Advancement of Science (AAAS).

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Thu, 28 Jan 2021 11:33:05 -0500 2021-02-10T16:00:00-05:00 2021-02-10T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Han Liang, PhD Professor and Deputy Chair, Department of Bioinformatics and Computational Biology Professor, Department of Systems Biology Barnhart Family Distinguished Professor in Targeted Therapies The University of Texas MD Anderson Cancer Center
RNA Seminar featuring: Karla Neugebauer, Yale University School of Medicine (February 15, 2021 4:00pm) https://events.umich.edu/event/78295 78295-20004839@events.umich.edu Event Begins: Monday, February 15, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_aZggyZ0yQcSPcJrsHloXjQ

ABSTRACT: My lab is interested in the coordination between transcription, RNA processing and nuclear organization that governs gene expression. We have established experimental systems in budding yeast, zebrafish embryos, and mammalian tissue culture cells to explore transcription and splicing regulation in a variety of biological contexts and with a diversity of tools, from imaging to genome-wide approaches. Our observations have provided novel insights into transcription and splicing mechanisms as well as principles of cellular organization that facilitate efficient gene expression. In this talk, I will be discussing rapid co-transcriptional splicing during erythropoiesis and how Cajal bodies assemble to ensure a steady supply of spliceosomal components.

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Lecture / Discussion Tue, 02 Feb 2021 16:32:41 -0500 2021-02-15T16:00:00-05:00 2021-02-15T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Prof. Karla Neugebauer, Ph.D.
Special Joint Seminar between our Department and the Genome Science Training Program (February 17, 2021 4:00pm) https://events.umich.edu/event/80415 80415-20719669@events.umich.edu Event Begins: Wednesday, February 17, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: The human genome sequence folds in three dimensions (3D) into a rich variety of locus-specific contact patterns. Despite growing appreciation for the importance of 3D genome folding in evolution and disease, we lack models for relating mutations in genome sequences to changes in genome structure and function. Towards that goal, we discovered that the organization of gene regulatory domains within chromosomes and the specific sequences that sit at boundaries between domains are under strong negative selection in the human population and over primate evolution. Motivated by this signature of functional importance, we developed a deep convolutional neural network, called Akita, that accurately predicts genome folding from DNA sequence alone. Representations learned by Akita underscore the importance of the structural protein CTCF but also reveal a complex grammar beyond CTCF binding sites that underlies genome folding. Akita enabled rapid in silico predictions for effects of sequence mutagenesis on the 3D genome, including differences in genome folding across species and in disease cohorts, which we are validating with CRISPR-edited genomes. This prediction-first strategy exemplifies my vision for a more proactive, rather than reactive, role for data science in biomedical research.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

Short bio: Dr. Katherine S. Pollard is Director of the Gladstone Institute of Data Science & Biotechnology, Investigator at the Chan Zuckerberg Biohub, Professor in the Department of Epidemiology & Biostatistics and Bioinformatics Graduate Program at UCSF. Her lab develops statistical models and open source bioinformatics software for the analysis of massive genomic datasets. Previously, Dr. Pollard was an assistant professor in the University of California, Davis Genome Center and Department of Statistics. She earned her PhD in Biostatistics from the University of California, Berkeley and was a comparative genomics postdoctoral fellow at the University of California, Santa Cruz. She was awarded the Thomas J. Watson Fellowship, the Sloan Research Fellowship, and the Alumna of the Year from UC Berkeley. She is a Fellow of the International Society for Computational Biology and of the California Academy of Sciences.

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Livestream / Virtual Wed, 06 Jan 2021 09:24:05 -0500 2021-02-17T16:00:00-05:00 2021-02-17T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Katherine S. Pollard, PhD (Director, Gladstone Institute of Data Science & Biotechnology; Professor, UCSF; Investigator, Chan Zuckerberg Biohub)
U-M Structure Seminar: "Design Principles for Site-Selective Hydroxylation in Paralytic Shellfish Toxin Biosynthesis" (February 19, 2021 10:00am) https://events.umich.edu/event/76158 76158-19669627@events.umich.edu Event Begins: Friday, February 19, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Jiayi Tian
Graduate Student
Bridwell-Rabb Lab
University of Michigan

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Livestream / Virtual Wed, 03 Feb 2021 10:59:01 -0500 2021-02-19T10:00:00-05:00 2021-02-19T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
CCMB / DCMB Weekly Seminar (February 24, 2021 4:00pm) https://events.umich.edu/event/82197 82197-21052530@events.umich.edu Event Begins: Wednesday, February 24, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: COVID Moonshot is an international consortium aiming to discover patent-free oral antiviral against SARS-CoV-2, targeting the main protease. Operating under an open science ethos, we make all data and structures publicly available, and crowdsource molecule designs from the community. In less than a year, we went from fragment hits to nanomolar leads in biochemical and antiviral assays. In my talk, I will discuss Moonshot’s journey towards orally bioavailable, non-covalent, and non-peptidomimetic Mpro inhibitors. I will discuss how machine learning technologies have accelerated our design-make-test cycle, and the learnings we gleaned from this large-scale prospective use of algorithms.

Bio: Dr. Alpha Lee is a Group Leader in the Department of Physics, University of Cambridge. His research focuses on developing machine learning technologies that close the design-make-test cycle for small molecule drug discovery and materials discovery. He is interested in how physical and chemical insights can be integrated into the design of interpretable algorithms. Before joining Cambridge, Dr. Lee was a Fulbright Scholar at Harvard and obtained his PhD from the University of Oxford.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Wed, 17 Feb 2021 13:18:31 -0500 2021-02-24T16:00:00-05:00 2021-02-24T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: "The structure adventures: from academia to industry" (February 26, 2021 10:00am) https://events.umich.edu/event/76180 76180-19671613@events.umich.edu Event Begins: Friday, February 26, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Yoana Dimitrova, Ph.D.
Structural Biology Scientist
Genentech

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Livestream / Virtual Thu, 04 Feb 2021 09:17:19 -0500 2021-02-26T10:00:00-05:00 2021-02-26T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: Melissa Moore, Moderna Therapeutics (March 3, 2021 4:00pm) https://events.umich.edu/event/81265 81265-20879904@events.umich.edu Event Begins: Wednesday, March 3, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

**Please register here for March 3rd seminar: https://umich.zoom.us/webinar/register/WN_l0kt_NjpRh-f33LJj7KGpA

Dr. Moore will address scientists and non-scientists, and will take live questions.

In her role as Chief Scientific Officer, Platform Research, Dr. Melissa Moore is responsible for leading mRNA biology, delivery and computation science research at Moderna. She joined Moderna in 2016 from the University of Massachusetts Medical School, where she served as Professor of Biochemistry & Molecular Pharmacology, Eleanor Eustis Farrington Chair in Cancer Research and a long-time Investigator at the Howard Hughes Medical Institute (HHMI). Dr. Moore was also a founding Co-Director of the RNA Therapeutics Institute (RTI) at UMassMed, and was instrumental in creating the Massachusetts Therapeutic and Entrepreneurship Realization initiative (MassTERi), a faculty-led program intended to facilitate the translation of UMMS discoveries into drugs, products, technologies and companies. Dr. Moore is an elected member of the National Academy of Sciences (2017) and a Fellow of the American Academy of Arts and Sciences (2019).

Dr. Moore holds a B.S. in Chemistry and Biology from the College of William and Mary, and a Ph.D. in Biological Chemistry from MIT, where she specialized in enzymology under Prof. Christopher T. Walsh. She began working on RNA metabolism during her postdoctoral training with Phillip A. Sharp at MIT. During her 23 years as a faculty member, first at Brandeis and then at UMassMed, her research encompassed a broad array of topics related to the roles of RNA and RNA-protein (RNP) complexes in gene expression, and touched on many human diseases including cancer, neurodegeneration, and preeclampsia.

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Lecture / Discussion Wed, 10 Feb 2021 19:47:49 -0500 2021-03-03T16:00:00-05:00 2021-03-03T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Melissa Moore, Ph.D., Moderna Therapeutics
U-M Structure Seminar: "Carbohydrate capture by human gut bacteria: the first crystal structure of raw starch-binding protein, Doc6, from Ruminococcus bromii" (March 5, 2021 10:00am) https://events.umich.edu/event/76727 76727-19741013@events.umich.edu Event Begins: Friday, March 5, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Amanda Photenhauer
Graduate Student
Nicole Koropatkin Lab
University of Michigan

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Livestream / Virtual Fri, 19 Feb 2021 09:48:44 -0500 2021-03-05T10:00:00-05:00 2021-03-05T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
CCMB / DCMB Weekly Seminar Series (March 10, 2021 4:00pm) https://events.umich.edu/event/82479 82479-21108092@events.umich.edu Event Begins: Wednesday, March 10, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Single-cell technologies have transformed biomedical research in the last few years. With single-cell sequencing, we can now simultaneously measure thousands of genomics features in a large number of cells, which provides an ultrahigh resolution phenotypic map for each individual. However, single-cell protocols are complex. Even with the most sensitive platforms, the data are often sparse and noisy. Recent development of single-cell multi-omics and spatial transcriptomics technologies further imposed additional challenges on data integration. In this talk, I will present several machine learning methods that my group recently developed for single-cell and spatial transcriptomics data analysis. I will discuss methods for simultaneous denoising, clustering and batch effect correction, single-cell multi-omics data integration, identification of spatially variable genes, generation of super-resolution gene expression, and inference of cell type distribution in spatial transcriptomics. I will illustrate our methods by showing results from ongoing collaborations on cardiometabolic disease and applications to brain and cancer data.
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Biography: Dr. Li’s research interests include statistical genetics and genomics, bioinformatics, and computational biology. The central theme of her current research is to use statistical and computational approaches to understand cellular heterogeneity in human-disease-relevant tissues, to characterize gene expression diversity across cell types, to study the patterns of cell state transition and crosstalk of various cells using data generated from single-cell and spatial transcriptomics studies, and to translate these findings to the clinics. In addition to methods development, Dr. Li is also interested in collaborating with researchers seeking to identify complex disease susceptibility genes and acting cell types. She is Director of Biostatistics for the Gene Therapy Program at Penn, where she advises biostatistics and bioinformatics analysis for various gene therapy studies. She is also Chair of the Graduate Program in Biostatistics. Dr. Li actively serves in the scientific community. She served as a regular member for the NIH Genomics, Computational Biology and Technology (GCAT) study section for 6 years, and the NHGRI Center for Inherited Disease Research (CIDR) for 3 years. She is an Associate Editor of Annals of Applied Statistics, Statistics in Biosciences, PLOS Computational Biology, and Human Genetics and Genomics Advances. She is an elected member of the International Statistical Institute and a Fellow of the American Statistical Association.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Wed, 24 Feb 2021 12:57:46 -0500 2021-03-10T16:00:00-05:00 2021-03-10T17:00:00-05:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: "Starch Recognition and Degradation by the Human Gut Symbiont Bacteroides ovatus" (March 12, 2021 10:00am) https://events.umich.edu/event/76185 76185-19671617@events.umich.edu Event Begins: Friday, March 12, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Haley Brown
Graduate Student
Koropatkin Lab
University of Michigan

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Livestream / Virtual Mon, 22 Feb 2021 14:03:25 -0500 2021-03-12T10:00:00-05:00 2021-03-12T11:00:00-05:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: James Nuñez, HHMI Hanna Gray Fellow, University of California, San Francisco (March 15, 2021 4:00pm) https://events.umich.edu/event/81286 81286-20881887@events.umich.edu Event Begins: Monday, March 15, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_f8wC8rrJQzuhYzTEXoW69Q


ABSTRACT
General approaches for heritably altering gene expression would enable many discovery and therapeutic efforts. I will present CRISPRoff— a programmable epigenetic memory writer consisting of a single dead Cas9 fusion protein that establishes DNA methylation and repressive histone modifications to turn off transcription. Transient CRISPRoff expression initiates highly specific DNA methylation and gene repression that is maintained through cell division and differentiation of stem cells to neurons. Pairing CRISPRoff with genome-wide screens and analysis of chromatin marks enabled us to explore the rules for heritable silencing. We identify sgRNAs capable of silencing the large majority of genes including those lacking canonical CpG islands (CGIs) and reveal a wide targeting window extending beyond annotated CGIs. Our finding that targeted DNA methylation outside of CGIs leads to memorized gene silencing expands the canonical model of methylation-based silencing and broadly enables diverse applications including genome-wide screens, multiplexed cell engineering, enhancer silencing, and mechanistic exploration of epigenetic inheritance.

KEYWORDS: CRISPR, transcription, epigenetics
Flyer in PDF: https://rna.umich.edu/wp-content/uploads/2021/02/Seminar-Flyer-03152021-Nunez.pdf

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Lecture / Discussion Thu, 18 Feb 2021 09:21:31 -0500 2021-03-15T16:00:00-04:00 2021-03-15T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion James Nunez, Ph.D. UCSF
CCMB / DCMB Weekly Seminar Series featuring Sriram Chandrasekaran (Assistant Professor, Biomedical Engineering) (March 17, 2021 4:00pm) https://events.umich.edu/event/82825 82825-21179592@events.umich.edu Event Begins: Wednesday, March 17, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Drug combinations have the potential to greatly expand our pharmacopeia while reducing both cost and drug resistance. Yet the current drug-discovery approach is unable to screen the astronomical number of possible combinations in different cell types and does not account for the complex environment inside the body. We have developed AI tools - INDIGO and MAGENTA - that predict the efficacy of drug combinations based on the properties of the drugs, the pathogen, and the infection environment. We are also using modeling to identify drugs that work in synergy with the host immune system. Using INDIGO and MAGENTA, we have identified highly synergistic combinations of repurposed drugs to treat drug resistant infections including Tuberculosis, the deadliest bacterial infection. INDIGO also accurately predicts the outcome of past clinical trials of drug combinations. Our ultimate goal is to create a personalized approach to treat infections using AI.
* * *
Biography: Chandrasekaran received his bachelor’s degree in Biotechnology from Anna University in 2008, and a PhD in Biophysics from the University of Illinois at Urbana-Champaign in 2013. He worked at Harvard University and MIT as a Harvard Junior Fellow between 2013 and 2016 and became an Assistant Professor at UM in 2017. His lab develops systems biology algorithms for drug discovery. Computer models from his lab like INDIGO and MAGENTA are being used to design effective therapies against drug resistant pathogens. His lab also develops systems biology algorithms to understand metabolic regulation. The approaches that they have created (PROM, ASTRIX, DFA, EGEM and GEMINI) perform complementary functions in modeling of metabolic and regulatory networks. Chandrasekaran’s research has been published in Cell, Genome Biology, mBio, and PNAS. For his work, Chandrasekaran previously received the 2013 Harvard Junior Fellowship, the 2011 Howard Hughes Medical Institute (HHMI) International Predoctoral Fellowship, the 2014 William Milton Fund award, 2018 UM Precision Health Investigator Award, and the 2018 Distinguished Young Investigator Award from the AICHE COBRA society.


https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Fri, 05 Mar 2021 14:44:14 -0500 2021-03-17T16:00:00-04:00 2021-03-17T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Sriram Chandrasekaran, PhD (Assistant Professor, Biomedical Engineering)
NeuroNetwork for Emerging Therapies Mini Symposium Series: Nutrition & Brain Health with The Henry Ford (March 18, 2021 2:00pm) https://events.umich.edu/event/82153 82153-21044613@events.umich.edu Event Begins: Thursday, March 18, 2021 2:00pm
Location: Off Campus Location
Organized By: NeuroNetwork for Emerging Therapies

"You are what you eat" is a common phrase that researchers and scientists are proving remarkably true. Unhealthy diets not only lead to obesity, but that obesity can even lead to cognitive decline, or a decreased ability to think.

The third installment of the NeuroNetwork for Emerging Therapies Mini Symposium Series will explore what unhealthy foods do to the nervous system, a historical look at the downhill trend of eating habits, and how everyone can find an optimal nutritional balance. These presentations will be followed by a question and answer session.

“Nutrition & Brain Health” is made possible by the generous support of Robert and Katherine Jacobs, who believe that informing people about healthy food options is critically important to the health of their community.

Eva Feldman, MD, PhD, Director of the NeuroNetwork for Emerging Therapies, will moderate the 30-minute mini symposium and discuss diet and brain health. Debra Reid, PhD, MA, Curator of Agriculture and the Environment at The Henry Ford, will discuss the history of the American diet and how urban residents obtained fresh fruits and vegetables from urban markets, such as the Central Farmers Market that is under reconstruction at Greenfield Village. Michigan Medicine Lead Dietitian Danielle Karsies, MS, RDN, will provide direction for how people can apply the information from Drs. Feldman and Reid to help them make better food choices.

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Conference / Symposium Tue, 16 Feb 2021 13:46:27 -0500 2021-03-18T14:00:00-04:00 2021-03-18T14:30:00-04:00 Off Campus Location NeuroNetwork for Emerging Therapies Conference / Symposium Nutrition & Brain Health with The Henry Ford
U-M Structure Seminar: “Structural basis for neutralization of viruses by human antibodies: implications for vaccine design.” (March 19, 2021 10:00am) https://events.umich.edu/event/81669 81669-20941452@events.umich.edu Event Begins: Friday, March 19, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Andrew Flyak, Ph.D.
Postdoctoral Scholar, Bjorkman Lab
California Institute of Technology

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Lecture / Discussion Wed, 03 Feb 2021 11:03:26 -0500 2021-03-19T10:00:00-04:00 2021-03-19T12:00:00-04:00 Off Campus Location U-M Structural Biology Lecture / Discussion UM Structure Seminars
CCMB / DCMB Weekly Seminar Series Featuring Duncan K. Ralph (Fred Hutchinson Cancer Research Center) (March 24, 2021 4:00pm) https://events.umich.edu/event/82733 82733-21169592@events.umich.edu Event Begins: Wednesday, March 24, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: Antibodies are an integral part of the adaptive immune response, and are a critical component of both vaccine-induced and naturally-acquired immunity. The development of deep sequencing approaches in recent years has allowed us to sample a significant fraction of the diverse repertoire of B cell receptor sequences from which antibodies are made. These sequences encode a wealth of information on the somatic rearrangement and evolutionary processes that determine the contours of our antibody repertoires, and thus our ability to respond appropriately to pathogens and vaccines. Extracting this information, however, requires a careful inference approach across several different analysis steps. I will describe the computational approaches that we have taken to solving these problems, which constitute the partis software package, and describe their application in several projects, including HIV and Dengue data.

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Biography: Duncan attended the University of California at Santa Cruz for his undergraduate studies in physics, completing his thesis on energy transport in condensed matter theory in 2005. He completed his PhD at the Massachusetts Institute of Technology in 2014, working on the Large Hadron Collider at the European particle physics laboratory (CERN). His thesis described the observation of Higgs boson decays to four leptons. Since 2014, he has worked in Frederick Matsen’s lab at the Fred Hutchinson Cancer Research Center, first as a postdoctoral researcher and more recently as a staff scientist, writing new computational methods for the analysis of B cell receptor deep sequencing data.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Thu, 04 Mar 2021 11:20:24 -0500 2021-03-24T16:00:00-04:00 2021-03-24T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
5th Annual RNA Symposium, "Processing RNA" (March 25, 2021 11:00am) https://events.umich.edu/event/80161 80161-20572609@events.umich.edu Event Begins: Thursday, March 25, 2021 11:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

FOR MORE DETAILS & ABSTRACTS VISIT: https://rna.umich.edu/2021-symposium/

Thursday, March 25, 2021
11:00 / Welcome
11:05 / KEYNOTE 1: Tracy Johnson, UCLA, “RNA Splicing, Chromatin Modification, and the Coordinated Control of Gene expression”
12:00 / Short break
12:10 / KEYNOTE 2: Kevin Weeks, UNC, “Structure-Based Discovery of New Functions in Large RNAs”
1:05 / Data Blitz: Cathy Smith, Daniel Peltier, Yan Zhang
1:35 / KEYNOTE 3: Feng Zhang, MIT, “Exploration of Biological Diversity to Discover Novel Molecular Technologies”
2:30 / Close Day 1

Friday, March 26, 2021
11:00 / Welcome
11:05 / KEYNOTE 4: Brenda Bass, University of Utah, “Distinguishing self and non-self dsRNA in vertebrates and invertebrates”
12:00 / Short break
12:10 / KEYNOTE 5: Christopher Lima, Sloan-Kettering Institute, “Mechanisms that target RNA for destruction”
1:05 / Data Blitz: Meredith Purchal, Adrien Chauvier, Shannon Wright
1:35 / Panel discussion with keynote speakers
2:30 / Close Day 2

Liveblogging by MiSciWriters! https://misciwriters.com/

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Lecture / Discussion Tue, 23 Mar 2021 15:03:26 -0400 2021-03-25T11:00:00-04:00 2021-03-25T14:30:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion 5th Annual RNA Symposium
UM Structure Seminar: "Structural Studies of the Mitochondrial GTPase, Miro1" (March 26, 2021 10:00am) https://events.umich.edu/event/76222 76222-19677551@events.umich.edu Event Begins: Friday, March 26, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Emily Eberhardt
Graduate Student
Michael Cianfrocco Lab
University of Michigan

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Livestream / Virtual Thu, 11 Mar 2021 11:02:29 -0500 2021-03-26T10:00:00-04:00 2021-03-26T11:00:00-04:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
5th Annual RNA Symposium, "Processing RNA" (March 26, 2021 11:00am) https://events.umich.edu/event/80161 80161-20572610@events.umich.edu Event Begins: Friday, March 26, 2021 11:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

FOR MORE DETAILS & ABSTRACTS VISIT: https://rna.umich.edu/2021-symposium/

Thursday, March 25, 2021
11:00 / Welcome
11:05 / KEYNOTE 1: Tracy Johnson, UCLA, “RNA Splicing, Chromatin Modification, and the Coordinated Control of Gene expression”
12:00 / Short break
12:10 / KEYNOTE 2: Kevin Weeks, UNC, “Structure-Based Discovery of New Functions in Large RNAs”
1:05 / Data Blitz: Cathy Smith, Daniel Peltier, Yan Zhang
1:35 / KEYNOTE 3: Feng Zhang, MIT, “Exploration of Biological Diversity to Discover Novel Molecular Technologies”
2:30 / Close Day 1

Friday, March 26, 2021
11:00 / Welcome
11:05 / KEYNOTE 4: Brenda Bass, University of Utah, “Distinguishing self and non-self dsRNA in vertebrates and invertebrates”
12:00 / Short break
12:10 / KEYNOTE 5: Christopher Lima, Sloan-Kettering Institute, “Mechanisms that target RNA for destruction”
1:05 / Data Blitz: Meredith Purchal, Adrien Chauvier, Shannon Wright
1:35 / Panel discussion with keynote speakers
2:30 / Close Day 2

Liveblogging by MiSciWriters! https://misciwriters.com/

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Lecture / Discussion Tue, 23 Mar 2021 15:03:26 -0400 2021-03-26T11:00:00-04:00 2021-03-26T14:30:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion 5th Annual RNA Symposium
CCMB / DCMB Weekly Seminar (March 31, 2021 4:00pm) https://events.umich.edu/event/83395 83395-21369780@events.umich.edu Event Begins: Wednesday, March 31, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:

Large, deeply phenotyped cohorts are reshaping the world of environmental epidemiology. Two such “big data” resources that are reshaping how we understand environmental health are electronic health records and human cohorts with genome-wide molecular phenotyping. Each provides a unique perspective that is moving the field closer towards “personalized” insights into environmental health risks. Here I will talk about a series of studies which utilize electronic health records and molecularly phenotyped cohorts to investigate vulnerable populations, gene-environment interactions, and epigenetic biomarkers of environmental sensitivity. Together these studies are helping us to understand environmental health risks in a new light.

Short bio:

Dr. Cavin Ward-Caviness is a Principal Investigator in the Public Health and Integrated Toxicology Division of the US Environmental Protection Agency. With a background in computational biology and environmental epidemiology, Dr. Ward-Caviness seeks to understand the environmental factors which influence health in vulnerable populations and the molecular mechanisms that influence environmental health risks. The Ward-Caviness lab uses a variety of “big data” approaches, and Dr. Ward-Caviness is the PI of the EPA CARES research resource, which allows researchers to study environmental health effects in vulnerable patient populations, e.g. individuals with heart failure, using large electronic health record databases. Dr. Ward-Caviness is also interested in how epigenetics and metabolomics can serve as an early indicator of adverse health effects from chemical and social environmental exposures and in particular how molecular biomarkers can give us insight into how the environment may accelerate the aging process and thus contribute to chronic disease. By integrating molecular and clinical data, Dr. Ward-Caviness seeks to understand environmental health as a way to advance personalized medicine and reduce health disparities.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Mon, 29 Mar 2021 15:15:11 -0400 2021-03-31T16:00:00-04:00 2021-03-31T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
RNA Seminar featuring: Natoya Peart, PhD, University of Pennsylvania (April 5, 2021 4:00pm) https://events.umich.edu/event/81288 81288-20881888@events.umich.edu Event Begins: Monday, April 5, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration required: https://umich.zoom.us/webinar/register/WN_0lUfePb0Qdac-cQZDpeiEQ


KEYWORDS: Alternative splicing, RNAMap, Esrp1

ABSTRACT: Coordinated regulation of alternative splicing is essential to the establishment of cell identity. The Epithelial Splicing Regulatory Proteins (Esrps), ESRP1 and ESRP2, are highly conserved paralogous proteins required for organogenesis of multiple organ systems and compromised function of Esrps contributes to human diseases and pathologies. Esrps are robustly expressed in the epithelial cells of the epidermis, large and small intestines, salivary glands, stomach, and a variety of other tissues, where they are vital in promoting an epithelial splicing network. Although ESRP1 and ESRP2 share partial functional redundancy, ESRP1 appears to play a larger role in regulating gene expression.
Using a combination of enhanced immunoprecipitation coupled with high throughput sequencing (eCLIP) in the epithelial cells of mouse epidermis and RNA sequencing analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2 we generate a map of Esrp1 binding to RNA. We show that ESRP1 regulates splicing primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In particular, we show that Esrp1 binding upstream of or withing alternatively spliced exons suppresses exon inclusion, whilst binding downstream of the non-constitutive exon promotes exon inclusion. In addition, we identified widespread binding of ESRP1 in 3’ and 5’ untranslated regions (UTRs) of genes enriched for epithelial cell function suggesting that it directly regulates post-transcriptional gene expression steps in addition to splicing.


If you are having difficulties registering, please contact Martina Jerant at mjerant@umich.edu

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Lecture / Discussion Mon, 08 Mar 2021 12:23:08 -0500 2021-04-05T16:00:00-04:00 2021-04-05T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Natoya Peart, PhD, University of Pennsylvania
Exploring the Modularity of Large Complexes Involved in Transcription Initiation and Chromatin Modifications-Martha Ludwig Lectureship (April 6, 2021 12:00pm) https://events.umich.edu/event/80656 80656-20769634@events.umich.edu Event Begins: Tuesday, April 6, 2021 12:00pm
Location: Off Campus Location
Organized By: Biological Chemistry

Dr. Eva Nogales, UC Berkeley, will present the annual Martha L. Ludwig Lectureship in Structural Biology on Tuesday April 6th, 2021 at 12:00pm

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Workshop / Seminar Tue, 12 Jan 2021 13:39:18 -0500 2021-04-06T12:00:00-04:00 2021-04-06T13:00:00-04:00 Off Campus Location Biological Chemistry Workshop / Seminar Nogales
CCMB / DCMB Weekly Seminar Series (April 7, 2021 4:00pm) https://events.umich.edu/event/83241 83241-21320453@events.umich.edu Event Begins: Wednesday, April 7, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract: More than 3,000 new Marine recruits were studied prospectively during their initial Marine-mandated two-week quarantine and their subsequent basic training at Parris Island. The COVID Health Action Response for Marines (CHARM) studied completed 20,000 study visits and obtained more than 70,000 biosamples including pre- to post- SARS-CoV-2 infections in more than 1000 recruits. Serological, transcriptomic, and epigenetic analyses identify the response signature to SARS-CoV-2 infection in these largely asymptomatic young adults. Phylogenetic analysis and modeling provide insight into epidemiology and guidance for public health measures.

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Specialty: Neurology

Research Topics: Addiction, Apoptosis/Cell Death, Basal Ganglia, Bioinformatics, Brain, Cellular Immunity, Cerebral Cortex, Mathematical and Computational Biology, Multiple Sclerosis, Neuro-degeneration/protection, Receptors, Reproductive Biology, Signal Transduction, Theoretical Biology, Vaccine Development, Viruses and Virology

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Tue, 23 Mar 2021 11:23:58 -0400 2021-04-07T16:00:00-04:00 2021-04-07T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: "Structural study of the Legionella pneumophila Dot/Icm T4SS using cryo-electron microscopy" (April 9, 2021 10:00am) https://events.umich.edu/event/76184 76184-19671616@events.umich.edu Event Begins: Friday, April 9, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Clarissa Durie, Ph.D.
Postdoctoral Fellow
Melanie Ohi Lab
University of Michigan

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Livestream / Virtual Thu, 25 Mar 2021 09:55:39 -0400 2021-04-09T10:00:00-04:00 2021-04-09T11:00:00-04:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
CCMB / DCMB Weekly Seminar (April 14, 2021 4:00pm) https://events.umich.edu/event/83595 83595-21436485@events.umich.edu Event Begins: Wednesday, April 14, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:
My lab's research involves the development and application of systems biology approaches—combining computation, machine learning, quantitative modeling, and experiments—to study the immune system in health and disease. Recent technological and computational advances allow comprehensive interrogation of multiple modalities (e.g., proteins, mRNAs, immune receptor sequences) in single cell resolution in the human population. Here I will highlight our work in the analysis human and single cell variations along the axes of early immune development, vaccination, and COVID-19. If time permits, I will also discuss the integration of tissue imaging, machine learning, and multiscale dynamical modeling of immune cell interactions to investigate the homeostatic regulation of autoreactive T cells.

* * *

Biography: Dr. Tsang is a senior investigator in the NIH Intramural Research Program and leads a laboratory focusing on systems and quantitative immunology at the National Institute of Allergy and Infectious Diseases (NIAID). He also co-directs the Trans-NIH Center for Human Immunology (CHI) and leads its research program in systems human immunology. Dr. Tsang trained in computer engineering and computer science at the University of Waterloo and received his Ph.D. in biophysics from Harvard University. Dr. Tsang has worked as a software engineer and pursued systems biology research in both academia and industry including Rosetta Inpharmatics, Caprion Proteomics, MIT, and Merck Research Laboratories. Dr. Tsang has won several awards for his research, including NIAID Merit Awards for the development of a data reuse and crowdsourcing platform OMiCC and for leading a system biology study of human immune variability and influenza vaccination, which was selected as a top NIAID Research Advances of 2014. He currently serves as the founding chief editor of systems immunology for Frontiers in Immunology. He has served as a scientific advisor for a number of programs and organizations including ImmPort (the clinical and molecular data repository for NIAID), the Committee on Precision Medicine for the World Allergy Organization, the NIAID Modeling Immunity for Biodefense Program, the Allen Institute, the Immuno-Epidemiology Program at the National Cancer Institute, and the Human Vaccines Project.

https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Wed, 07 Apr 2021 08:59:05 -0400 2021-04-14T16:00:00-04:00 2021-04-14T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
RNA Seminar featuring: Jailson (Jay) Brito Querido, Ph.D. MRC Laboratory of Molecular Biology, Cambridge, UK (April 19, 2021 4:00pm) https://events.umich.edu/event/81408 81408-20893767@events.umich.edu Event Begins: Monday, April 19, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_78YYOhIhTbOBy2_JSdM7Wg

ABSTRACT: A key step in translational initiation is the recruitment of the 43S pre-initiation complex (43S PIC) by the cap-binding complex (eIF4F) at the 5´ end of mRNA. Eukaryotic initiation factors eIF1, eIF1A, eIF3, eIF5, and the ternary complex (TC) of eIF2–GTP–tRNAiMet bind to the 40S ribosomal subunit to form the 43S PIC. Once assembled, the 43S PIC is recruited to the cap-binding complex eIF4F at the 5´end of mRNA to form a 48S initiation complex (48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we determined the structure of a reconstituted human 48S using cryo-electron microscopy. The structure reveals insights into early events of translation initiation complex assembly. It reveals how eIF4F interacts with subunits of the eIF3 structural core near the mRNA exit channel in the 43S. The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests a “blind-region” that would preclude recognition of start sites upstream of the location of the P site at the point of recruitment.

KEYWORDS: mRNA, ribosome, eIF4F, eIF4A, translation

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Lecture / Discussion Tue, 13 Apr 2021 12:58:40 -0400 2021-04-19T16:00:00-04:00 2021-04-19T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Jailson (Jay) Brito Querido, Ph.D.
Special Joint Seminar between DCMB, Mathematics, MIDAS, and Smale Institute (April 22, 2021 1:00pm) https://events.umich.edu/event/83615 83615-21491327@events.umich.edu Event Begins: Thursday, April 22, 2021 1:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:

The quest to understand consciousness, once the purview of philosophers and theologians, is now actively pursued by scientists of many stripes. This talk looks at consciousness from the perspective of theoretical computer science. It formalizes the Global Workspace Theory (GWT) originated by cognitive neuroscientist Bernard Baars and further developed by him, Stanislas Dehaene, and others. Our major contribution lies in the precise formal definition of a Conscious Turing Machine (CTM), also called a Conscious AI. We define the CTM in the spirit of Alan Turing’s simple yet powerful definition of a computer, the Turing Machine (TM). We are not looking for a complex model of the brain nor of cognition but for a simple model of (the admittedly complex concept of) consciousness. After formally defining CTM, we give a formal definition of consciousness in CTM. We then suggest why the CTM has the feeling of consciousness. The reasonableness of the definitions and explanations can be judged by how well they agree with commonly accepted intuitive concepts of human consciousness, the range of related concepts that the model explains easily and naturally, and the extent of its agreement with scientific evidence.

https://umich.zoom.us/j/95135773568

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Livestream / Virtual Wed, 14 Apr 2021 10:17:45 -0400 2021-04-22T13:00:00-04:00 2021-04-22T14:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: "Structure and substrate selection of Saccharomyces cerevisiae pseudouridine synthase 7" (April 23, 2021 10:00am) https://events.umich.edu/event/76221 76221-19677550@events.umich.edu Event Begins: Friday, April 23, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Meredith Purchal
Graduate Student
Markos Koutmos Lab
University of Michigan

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Livestream / Virtual Fri, 02 Apr 2021 10:25:40 -0400 2021-04-23T10:00:00-04:00 2021-04-23T11:00:00-04:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: Olivia Rissland, University of Colorado School of Medicine (May 3, 2021 4:00pm) https://events.umich.edu/event/81302 81302-20881902@events.umich.edu Event Begins: Monday, May 3, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration Required: https://umich.zoom.us/webinar/register/WN_vA9zYS5nSEenf8Zmt1f-qA


ABSTRACT: The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of the Drosophila CTLH complex suggests that substrate recognition is different than orthologous complexes. Despite occurring hours earlier, egg activation mediates clearance of these proteins through the Pan Gu kinase, which stimulates translation of Kondo mRNA. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT.

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Lecture / Discussion Fri, 02 Apr 2021 16:07:11 -0400 2021-05-03T16:00:00-04:00 2021-05-03T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Olivia Rissland, Ph.D.
U-M Structure Seminar: "Investigation of RNA 3D Structure & Small Molecule Interactions by a Multidisciplinary Approach" (May 7, 2021 10:00am) https://events.umich.edu/event/77785 77785-19931610@events.umich.edu Event Begins: Friday, May 7, 2021 10:00am
Location: Off Campus Location
Organized By: U-M Structural Biology

Elizabeth Tidwell
Graduate Student
Koutmos Lab
University of Michigan

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Livestream / Virtual Thu, 22 Apr 2021 10:28:36 -0400 2021-05-07T10:00:00-04:00 2021-05-07T11:00:00-04:00 Off Campus Location U-M Structural Biology Livestream / Virtual UM Structure Seminars
RNA Seminar featuring: Thomas Martinez, Salk Institute for Biological Studies (May 17, 2021 4:00pm) https://events.umich.edu/event/81303 81303-20881903@events.umich.edu Event Begins: Monday, May 17, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration Required: https://umich.zoom.us/webinar/register/WN_90RkcQTGQZa7ifQ8kbSdNQ

KEYOWORDS: microprotein, smORF, ribosome profiling

ABSTRACT: Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. Several smORF-encoded microproteins have been characterized and implicated in a variety of critical processes, including regulation of mRNA decay, DNA repair, and muscle formation. Thus, rigorous and comprehensive annotation of protein-coding smORFs is critical to our understanding of basic biology and physiology, as well as disease. We recently developed an improved workflow that integrates de novo transcriptome assembly and ribosome profiling to overcome obstacles with previous methods to more confidently annotate thousands of novel smORFs across multiple human cell lines, including hundreds encoded on putative non-coding RNAs. Over 1,500 smORFs are found in two or more cell lines, and ~40% lack a canonical AUG start codon. Evolutionary conservation analyses suggest that hundreds of smORF-encoded microproteins are likely functional. We also find that smORF-derived peptides are detectable on human leukocyte antigen complexes, positioning smORFs as a source of novel antigens. The annotation of protein-coding smORFs radically alters the current view of the human genome’s coding capacity and will provide a rich pool of unexplored, functional human genes.

BIO: Thomas received his B.S. in Biological Engineering from MIT and trained in Prof. JoAnne Stubbe’s laboratory, where he studied the mechanism of ribonucleotide reductase. He then recieved his Ph.D. in Biochemistry & Molecular Biophysics from Caltech as an NIH NRSA predoctoral fellow under the mentorship of Prof. Peter Dervan. His thesis work focused primarily on characterizing the effects of DNA binding pyrrole-imidazole polyamides on DNA replication in prostate cancer cells. Thomas is currently an NIH NRSA postdoctoral fellow in Prof. Alan Saghatelian’s laboratory, where he has developed an integrative platform combining ribosome profiling and de novo transcriptome assembly to discover functional smORF encoded microproteins in the human genome.

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Lecture / Discussion Wed, 14 Apr 2021 12:39:54 -0400 2021-05-17T16:00:00-04:00 2021-05-17T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Thomas Martinez, Salk Institute for Biological Studies
RNA Innovation Seminar featuring Rising Scholars: Khan & McMillan (June 14, 2021 4:00pm) https://events.umich.edu/event/83934 83934-21619166@events.umich.edu Event Begins: Monday, June 14, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration Required: https://umich.zoom.us/webinar/register/WN_uLz-ONHVQPuRINMYUNvBJQ

“CCR5 as a model to examine reporter assays in evaluating translational phenomena”
Yousuf Khan
Knight-Hennessy Scholar
Stanford University

KEYWORDS: dual luciferase, frameshifting, recoding, CCR5
ABSTRACT: During the decoding of a subset of mRNAs, a proportion of ribosomes productively shift to the −1 reading frame at specific slippage-prone sites in a phenomenon known as programmed −1 ribosomal frameshifting (−1 PRF) to generate a frameshifted, C-terminally unique protein. The first experimentally verified occurrence of functionally utilized non-retroelement derived −1 PRF in humans has been reported in the mRNA encoding the immune-functioning C-C chemokine receptor 5 (CCR5). Here, we show that frameshifting does not occur during CCR5 decoding. Apart from its importance in understanding expression of a gene relevant to cancer, an HIV-1 receptor (and the associated claimed rationale for generating the first humans derived from genetically modified embryos), the findings imply that caution is appropriate in assessing results from translational reporter assays.

~and~

“Intersection between RNA methylation and TDP43-mediated toxicity in ALS”
Michael McMillan
Ph.D. candidate
Cellular and Molecular Biology
University of Michigan

KEYWORDS: TDP43, m6A, ALS, RNA stability
ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease resulting in the death of upper and lower motor neurons. ALS has no known cure and limited therapeutic options, and the underlying pathological mechanisms remain unclear. Despite considerable variability in clinical presentation, over 95% of ALS cases exhibit cytoplasmic inclusions of the RNA binding protein TDP43. Emerging evidence suggests that TDP43 is crucial for RNA stability, and that dysregulation of RNA homeostasis may contribute to ALS pathogenesis.
Methylation of RNA at the 6th position nitrogen (N6-methyladenosine methylation, or m6A) by methyltransferases (writers) or removal of methyl groups by demethylases (erasers) has dramatic effects on RNA stability and translation mediated by a family of RNA biding proteins that recognize methylated RNA (readers). m6A writers and erasers specifically localize to nuclear speckles, membraneless nuclear organelles rich in RNA binding proteins and splicing factors, including TDP43. Together with our data showing that TDP43 regulates RNA stability, these observations suggest that TDP43 may destabilize m6A modified RNA. Here, we show that methylated RNA co-purified with TDP43 from cultured cells via RNA immunoprecipitation, and abrogation of methylation sites disrupted TDP43 binding, suggesting that TDP43 recognizes m6A modified RNA in cellulo. We also noted profound and widespread hypermethylation of coding and non-coding transcripts in ALS spinal cord, many overlapping with confirmed TDP43 target transcripts. Consistent with a central role for m6A modification in TDP43-mediated toxicity, we identified several factors operating within the m6A pathway that enhance or suppress the toxicity of TDP43 in rodent primary cortical neurons via a single-cell CRISPR/Cas9 candidate-based screen. Genetic knockout of the established m6A reader YTHDF2 rescued TDP43 toxicity in primary neurons, and YTHDF2 was also upregulated in ALS postmortem sections. Together, these data imply a fundamental link between m6A RNA modifications and ALS pathogenesis, potentially mediated by TDP43-dependent RNA destabilization.

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Lecture / Discussion Tue, 18 May 2021 14:31:45 -0400 2021-06-14T16:00:00-04:00 2021-06-14T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Yousuf Khan (Stanford) & Mike McMillan (U-M)
UM Single Cell Spatial Analysis Program (SCSAP) Kickoff Symposium (June 22, 2021 1:00pm) https://events.umich.edu/event/84222 84222-21620781@events.umich.edu Event Begins: Tuesday, June 22, 2021 1:00pm
Location: Off Campus Location
Organized By: Single Cell Spatial Analysis Program (SCSAP)

The UM BSI SINGLE CELL SPATIAL ANALYSIS PROGRAM KICK OFF SYMPOSIUM

Featuring Keynote Speaker Tzumin Lee, M.D. PhD.
Presenting: Linking single-cell genomics with single-cell genetics.

Date: June 22nd
Time: 1:00 pm -4:30 PM EST
Location: Zoom Webinar
Register at: https://umich.zoom.us/webinar/register/WN_Zax2iT5TReGILR_sQmIZ3w

Additional Mini-talks on: Spatial Transcriptomics, Single Cell RNA-Seq, CyTOF, Multispectral Imaging, Seq-SCOPE, Rare Cell Isolation.

Speakers:
Roger Cone, Ph.D. Evan Keller, Ph.D.
Thomas Wilson, M.D., Ph.D. Jun Li, Ph.D.
Tim Frankel, M.D. Sue Hammoud, Ph.D.
Jun Hee Lee, Ph.D. Olivia Koues, Ph.D.
Sunitha Nagrath, Ph.D. Justin Colacino, Ph.D.
Arvind Rao, Ph.D. Max S. Wicha, M.D.
Patricia Schnepp, Ph.D.

Find us at https://singlecellspatialanalysis.umich.edu
Questions/Comments please contact us at singlecellspatialanalysis@umich.edu

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Workshop / Seminar Fri, 04 Jun 2021 13:26:44 -0400 2021-06-22T13:00:00-04:00 2021-06-22T16:30:00-04:00 Off Campus Location Single Cell Spatial Analysis Program (SCSAP) Workshop / Seminar Dr. Tzumin Lee
RNA Collaborative Seminar (June 30, 2021 4:00pm) https://events.umich.edu/event/84166 84166-21620522@events.umich.edu Event Begins: Wednesday, June 30, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_6OEQ6sDAQ0-21GHm6d7VEQ

“Dynamic multivalent interactions drive mammalian RNA regulation”
Sethu Pitchiaya, Ph.D.
Dept of Urology

and

"Characterizing cellular RNA-protein interaction networks with chemical probes"
Chase Weidmann, Ph.D.
Dept of Biological Chemistry

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Lecture / Discussion Wed, 09 Jun 2021 15:28:29 -0400 2021-06-30T16:00:00-04:00 2021-06-30T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Sethu Pitchiaya & Chase Weidmann
Department of Computational Medicine & Bioinformatics || Weekly Seminar Series (September 8, 2021 4:00pm) https://events.umich.edu/event/86237 86237-21632210@events.umich.edu Event Begins: Wednesday, September 8, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:

Structural variants (SVs) are a source of pathogenic variants in a clinical referral population, however, they are often under-reported due to technical limitations of detection and difficulty with clinical interpretation. For example, mobile element insertions (MEIs) are estimated to lead to a positive finding in 1 out of 1000 rare genetic disease cases, yet the numbers are far lower in clinical diagnostic laboratories. Targeted NGS with short insert size libraries, unlike genome sequencing, will have very few discordant read pairs to indicate the presence of an SV. We, therefore, developed an SV detection tool called SCRAMble (Soft Clipped Read Alignment Mapper) to identify SV breakpoints in targeted NGS.

We applied SCRAMble to a prospective clinical referral cohort for exome sequencing to identify deletions and MEIs. We also applied SCRAMble to a hereditary cancer panel assay for the identification of a large inversion involving the MSH2 gene that causes Lynch syndrome. Adding breakpoint detection to clinical targeted sequencing identifies positive findings which were missed by prior testing and by other variant callers. Detecting breakpoints allows for more precise interpretation and for more targeted confirmation assays. By applying SV breakpoint detection, we are able to diagnose ~0.3% more cases. While this is a modest gain in diagnostic yield, for the patients and families involved, a positive diagnosis, even after prior testing, can have a meaningful impact on their lives.

Zoom link: https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Thu, 02 Sep 2021 14:28:18 -0400 2021-09-08T16:00:00-04:00 2021-09-08T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Rebecca Torene, Associate Director of Genomics Research | Data Science at GeneDx
RNA Innovation Seminar (September 13, 2021 4:00pm) https://events.umich.edu/event/86155 86155-21631746@events.umich.edu Event Begins: Monday, September 13, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

"Recent improvements in modeling and design of RNA-only structures"

ABSTRACT: The discovery and design of biologically important RNA molecules is outpacing three-structural characterization. I'll describe results from my and Wah Chiu's groups that demonstrate that cryo-electron microscopy can resolve maps of several kinds of RNA-only systems. These maps enable subnanometer-resolution 3D coordinate estimation when complemented with multidimensional chemical mapping and Rosetta DRRAFTER computational modeling. If time allows, I'll describe work from the Eterna project to stabilize mRNA molecules to help accelerate worldwide COVID immunization.

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Lecture / Discussion Thu, 02 Sep 2021 12:54:16 -0400 2021-09-13T16:00:00-04:00 2021-09-13T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Rhiju Das, Stanford University
Department of Computational Medicine & Bioinformatics Weekly Seminar Series (September 15, 2021 4:00pm) https://events.umich.edu/event/86598 86598-21635116@events.umich.edu Event Begins: Wednesday, September 15, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:

Chromosomal instability (CIN) results in the accumulation of large-scale losses, gains, and rearrangements of DNA. The broad genomic complexity caused by CIN is a hallmark of cancer, however, there is no systematic framework to measure different types of CIN and their impact on clinical phenotypes. Here, we evaluate the extent, diversity and origin of chromosomal instability across 7,880 tumors representing 33 cancer types from the TCGA collection. We present a compendium of 17 copy number signatures characterizing specific types of CIN, with putative aetiologies supported by multiple independent data sources. The signatures predict drug response and identify new drug targets. Our framework refines the understanding of impaired homologous recombination, one of the most therapeutically targetable types of CIN. Our results illuminate a fundamental structure underlying genomic complexity and provide a resource to guide future CIN
research in human cancers.

Bio:

Florian Markowetz is a Senior Group Leader at the Cancer Research UK Cambridge Institute. He is a Royal Society Wolfson Research Merit Award holder and received a CRUK Future Leader in Cancer Research prize. He holds degrees in Mathematics (Dipl. math.) and Philosophy (M.A.) from the University of Heidelberg and a Dr. rer. nat. (PhD equivalent) in Computational Biology from Free University Berlin, for which he was awarded an Otto-Hahn Medal by the Max Planck Society. His group at the CRUK Cambridge Institute combines computational work on cancer evolution and image analysis of the tumor tissue with experimental work on understanding key cancer mechanisms like the estrogen receptor.

Zoom link: https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Thu, 09 Sep 2021 11:24:05 -0400 2021-09-15T16:00:00-04:00 2021-09-15T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual Florian Markowetz (Senior Group Leader at the Cancer Research UK Cambridge Institute)
U-M Structure Seminar: "Structural basis for redox sensing by the cyanobacterial transcription regulator RexT" (September 17, 2021 10:00am) https://events.umich.edu/event/85431 85431-21626418@events.umich.edu Event Begins: Friday, September 17, 2021 10:00am
Location: Life Sciences Institute
Organized By: U-M Structural Biology

Bin Li, Ph.D.
Postdoctoral Research Fellow
University of Michigan, Bridwell-Rabb Lab

Hybrid: LSI Library and Zoom - https://umich.zoom.us/j/97763780708 (Password: structure)

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Workshop / Seminar Tue, 07 Sep 2021 14:09:31 -0400 2021-09-17T10:00:00-04:00 2021-09-17T11:00:00-04:00 Life Sciences Institute U-M Structural Biology Workshop / Seminar U-M Structure
Department of Computational Medicine & Bioinformatics Weekly Seminar (September 22, 2021 4:00pm) https://events.umich.edu/event/87282 87282-21640718@events.umich.edu Event Begins: Wednesday, September 22, 2021 4:00pm
Location: Off Campus Location
Organized By: DCMB Seminar Series

Abstract:

Histones are small proteins that package DNA into chromosomes, and a large number of studies have showed that several post-translational modification (PTM) sites on the histones are associated with both gene activation and silencing. Along with DNA and small non-coding RNA, histone PTMs make up epigenetic mechanisms that control gene expression patterns outside of DNA sequence mutations. Dysregulation of these chromatin networks underlie several human diseases such as cancer. Here I will give an update on technology advancements that have allowed for high-throughput quantitative analyses of histone PTMs and chromatin structure, and how we are applying these methods to understand epigenetic reprogramming found in malignant peripheral nerve sheath tumors (MPNSTs). MPNST is an aggressive sarcoma with recurrent loss of function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying complex involved in transcriptional silencing.

Zoom Link: https://umich-health.zoom.us/j/93929606089?pwd=SHh6R1FOQm8xMThRemdxTEFMWWpVdz09

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Livestream / Virtual Mon, 20 Sep 2021 15:27:41 -0400 2021-09-22T16:00:00-04:00 2021-09-22T17:00:00-04:00 Off Campus Location DCMB Seminar Series Livestream / Virtual
U-M Structure Seminar: "Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites (September 24, 2021 10:00am) https://events.umich.edu/event/85432 85432-21626419@events.umich.edu Event Begins: Friday, September 24, 2021 10:00am
Location: Life Sciences Institute
Organized By: U-M Structural Biology

Jayakrishnan Nandakumar, Ph.D.
University of Michigan
Associate Professor of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts

Hybrid: LSI Library and Zoom - https://umich.zoom.us/j/97763780708 (Password: structure)

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Workshop / Seminar Tue, 07 Sep 2021 14:09:51 -0400 2021-09-24T10:00:00-04:00 2021-09-24T11:00:00-04:00 Life Sciences Institute U-M Structural Biology Workshop / Seminar U-M Structure
Picture a Scientist (September 24, 2021 12:00pm) https://events.umich.edu/event/86730 86730-21639091@events.umich.edu Event Begins: Friday, September 24, 2021 12:00pm
Location: Off Campus Location
Organized By: Biostatistics

Please join us virtually on Friday, September 24th to watch and discuss the film, Picture a Scientist! This groundbreaking documentary chronicles the lives of three women scientists, who share their own experiences with sexual harassment and discrimination in order to create a more equitable and welcoming field. Watch the movie any time through this link, or join us for an online watch party at 9:30am. Then tune in at noon, to listen to a student-moderated discussion by our distinguished panel members, Dr. Patricia Coleman-Burns, Heather Colohan, Dr. Reshma Jagsi and Dr. Anna Kirkland. This will be followed by breakout room discussions (same registration as for the panel discussion) at 1:05 pm for students, staff, faculty and mixed groups.
https://sph.umich.edu/biostat/biostat_dei/biostat_dei_events/index.html

PANEL DISCUSSION (12 - 1PM ET)

Patricia W. Coleman-Burns, PhD, MA, U-M University of Michigan assistant professor emerita of nursing and Black studies. In addition to co-chairing the UM Academic Women's Caucus and serving on the U-M Women of Color in the Academy Project Steering Committee, she has served on the board of Safehouse Center on domestic violence and sexual assault. Her research, including her GENESIS pipeline project and EPIC Feedback Model, focuses on Black racial identity, workforce diversity, and reducing health disparities.

Heather Colohan, LMSW, U-M Sexual Assault Prevention and Awareness Center (SAPAC) Educator and Program Manager for Community Outreach & Systems Advocacy. She provides support and educational workshops to students, staff and faculty affected by sexual assault. She also supervises Raise the Bar; a program that works with local bars and transportation services to provide tailored workshops on sexual assault and bystander intervention.

Reshma Jagsi, MD, DPhil, Michigan Medicine Deputy Chair of Radiation Oncology, Newman Family Professor of Radiation Oncology, Residency Program Director, and Director of the Center for Bioethics and Social Sciences. Her many contributions to the study of gender discrimination in medicine include JAMA articles Gender Differences in the Salaries of Physician Researchers, and Sexual Harassment and Discrimination Experiences of Academic Medical Faculty.

Anna Kirkland, PhD, JD, U-M LSA Arthur F. Thurnau Professor of Women’s Studies, Director, Women’s and Gender Studies and School of Public Health Professor in Health Management and Policy by courtesy appointment. Prof. Kirkland served as a committee member on the National Academies panel charged with studying sexual harassment in the STEM fields of academia, published in June 2018 as Sexual Harassment of Women: Climate, Culture, and Consequences in Academic Sciences, Engineering, and Medicine.

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Lecture / Discussion Fri, 17 Sep 2021 11:10:58 -0400 2021-09-24T12:00:00-04:00 2021-09-24T13:00:00-04:00 Off Campus Location Biostatistics Lecture / Discussion Picture a scientist