Happening @ Michigan https://events.umich.edu/list/rss RSS Feed for Happening @ Michigan Events at the University of Michigan. Biophysics Virtual Seminar Series (October 2, 2020 12:00pm) https://events.umich.edu/event/77871 77871-19939555@events.umich.edu Event Begins: Friday, October 2, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

*Please see below for link to join the Zoom event. Passcode: Biophysics*

The Biophysics Virtual Seminar Series Presents:

Nirupama Sumangala - Biophysics Ph.D. Candidate (Ramamoorthy Group)

"Lipid Membrane Plays an Important Role for Facilitating Electron Transfer in Cytochrome P450"

Abstract: Cytochrome P450s (CYP450s) are a ubiquitous superfamily of enzymes that play a vital role in the metabolism of many exogenous and endogenous substrates including over 70% of the drugs on the market. For the catalytic reaction, CYP450 requires two electrons to be subsequently delivered, with the first one coming from cytochrome P450 reductase (CPR) and the second one from either CPR or cytochrome b5 (cytb5). We are interested in understanding the role of membrane in mediating the electron transfer from redox partners to CYP450. Our findings reveal that the lipid membrane is crucial to mediate a productive CYP450-CPR complex for electron transfer. Our data emphasizes the importance of studying the structure, dynamics and kinetics of CYP450 metabolon in a biologically relevant membrane mimetic system.

Keanu Guardiola Flores - Biophysics Ph.D. Candidate (Wood Group)

"Drug Effects on *Enterococcus Faecalis* Biofilms: Growth, Topology, and Population Dynamics"

Abstract: The emergence of antibiotic resistance poses a growing threat to public health and increasingly limits our ability to treat and control infections. Recently, researchers have shifted their focus to length scales where ecological and evolutionary dynamics of bacterial communities highlight new approaches for slowing resistance with currently available drugs. By combining confocal microscopy with simple mathematical models I will show how antibiotics shape the composition of biofilms as well as their spatial architecture at the single-cell level. Our results suggest that in spatially structured populations, which may more accurately reflect natural bacterial communities, the selection of resistance is not a simple result of homogenous selections but depends critically on the spatial arrangement of cells.

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Livestream / Virtual Tue, 29 Sep 2020 08:47:28 -0400 2020-10-02T12:00:00-04:00 2020-10-02T13:00:00-04:00 Off Campus Location LSA Biophysics Livestream / Virtual
Biophysics Virtual Seminar Series (October 9, 2020 12:00pm) https://events.umich.edu/event/76961 76961-19782523@events.umich.edu Event Begins: Friday, October 9, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

*Please see below for the link to join the Zoom livestream*

The Biophysics Virtual Seminar Series Presents:

Hong Qian - Olga Jung Wan Endowed Professor of Applied Mathematics, Department of Applied Mathematics, University of Washington

“A Mathematical Principle of Stochastic Chemical Kinetics and
Emergent Chemical Thermodynamics that Applies to Living Cells”

Abstract: In contrast to featureless point masses in Mechanics, a macromolecule in biochemistry has a large number of internal degrees of freedom in terms of atoms. The behavior of even a single protein in an aqueous environment, is often so complex that the mathematical representation of biochemical kinetics has to be statistical. In this talk, I present a stochastic formulation of general chemical reaction systems, with *N* species and *M* stochastic elementary reactions in solution and show how J. W. Gibbs’ macroscopic equilibrium chemical thermodynamics can be derived as a mathematical result, with an entropic force as its center piece. Our theory is actually applicable to mesoscopic open chemical systems with a chemostat, such as a single living cell. I then discuss the application of this theory to understand the notion of non-genetic phenotype switching, in terms of a landscape, in cell differentiation and cancer heterogeneity.

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Livestream / Virtual Fri, 09 Oct 2020 10:27:08 -0400 2020-10-09T12:00:00-04:00 2020-10-09T13:00:00-04:00 Off Campus Location LSA Biophysics Livestream / Virtual Zoom Passcode: Biophysics
Biophysics Seminar Series (October 16, 2020 12:00pm) https://events.umich.edu/event/77916 77916-19941582@events.umich.edu Event Begins: Friday, October 16, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

*Please see below for the link to join the Zoom event.*

The Biophysics Virtual Seminar Series presents:

Dr. Jamie Cate - Professor of Molecular & Cell Biology, and Chemistry,
University of California - Berkeley

“Selective modulation of human translation: potential for new therapeutics”

ABSTRACT: Small molecules that target the ribosome such as antibiotics generally impact a substantial fraction of the proteome. We recently identified a class of small molecules that bind the human ribosome and selectively stall the translation of a small subset of proteins. I will present biochemical and cell-based experiments, along with structures of human ribosome nascent chain complexes (RNCs) stalled by these compounds, determined by cryo-electron microscopy (cryo-EM). These small molecules bind in the ribosome exit tunnel in a eukaryotic-specific pocket formed by the 28S ribosomal RNA (rRNA) and arrest the translating ribosome through their interactions with the growing polypeptide chain. Intriguingly, a given compound can either inhibit or enhance translation, depending on the sequence of the protein nascent chain. These results begin to reveal how small molecules can be made to control human translation and suggest a new strategy for developing small molecules that selectively inhibit or enhance the production of proteins previously considered “undruggable.”

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Livestream / Virtual Thu, 08 Oct 2020 12:47:14 -0400 2020-10-16T12:00:00-04:00 2020-10-16T13:00:00-04:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Jamie Cate
Biophysics Seminar Series (October 23, 2020 12:00pm) https://events.umich.edu/event/77918 77918-19941583@events.umich.edu Event Begins: Friday, October 23, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

*Please see below for the link to join the Zoom event.*

The Biophysics Virtual Seminar Series presents:

Dr. Sandra Schmid - Chief Scientific Officer, Chan Zuckerberg Biohub

“Dynamin: A catalyst for fission, collaboration and controversy”

ABSTRACT: Kazuo Ikeda’s beautiful electron micrographs of neuromuscular junctions of Drosophila *shibire* mutants revealed the presence of collar-like structures around the necks of trapped endocytic intermediates. They inspired my 30 year-long obsession with dynamin, the mammalian homologue of *shibire.* Our subsequent studies of dynamin, which began in the early 90s provide benefitted from the development of new technologies and from interdisciplinary collaboration. I’ll describe the twists and turns of our efforts to understand the mechanisms underlying dynamin-catalyzed fission, the value of interdisciplinary collaborations, and the importance of taking all data into account when formulating models. I’ll detail our current understanding of dynamin-catalyzed fission, now supported by independent studies of others, and briefly describe the many remaining unanswered questions, keeping in mind (in the words of George Box) that, *“All models are wrong, but some are useful."*

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Livestream / Virtual Mon, 19 Oct 2020 15:12:59 -0400 2020-10-23T12:00:00-04:00 2020-10-23T13:00:00-04:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Sandra Schmid
Biophysics Seminar Series (October 30, 2020 12:00pm) https://events.umich.edu/event/77919 77919-19941584@events.umich.edu Event Begins: Friday, October 30, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

Join us on Zoom: https://umich.zoom.us/j/91037518250

The Biophysics Virtual Seminar Series presents:

Dr. Ido Golding - Professor of Physics, School of Molecular & Cellular Biology, University of Illinois Urbana-Champaign

"Illuminating bacterial individuality"

ABSTRACT: Single-cell measurements of mRNA copy numbers inform our understanding of stochastic gene expression, but these measurements coarse-grain over the individual copies of the gene, where transcription and its regulation take place stochastically. We recently combined single-molecule quantification of mRNA and gene loci to measure the transcriptional activity of an endogenous gene in
individual Escherichia coli bacteria. When interpreted using a theoretical model for mRNA dynamics, the single-cell data allowed us to obtain the probabilistic rates of promoter switching, transcription initiation and elongation, mRNA release and degradation. Unexpectedly, we found that gene activity can be strongly coupled to the transcriptional state of another copy of the same gene present in the cell, and to the event of gene replication during the bacterial cell cycle. These gene-copy and cell-cycle correlations demonstrate the limits of mapping whole-cell mRNA numbers to the underlying stochastic gene activity and highlight the contribution of previously hidden variables to the observed population heterogeneity.

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Livestream / Virtual Mon, 26 Oct 2020 09:26:15 -0400 2020-10-30T12:00:00-04:00 2020-10-30T13:00:00-04:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Ido Golding
Biophysics Seminar Series (November 6, 2020 12:00pm) https://events.umich.edu/event/77920 77920-19941585@events.umich.edu Event Begins: Friday, November 6, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Virtual Seminar Series presents:

Dr. Nozomi Ando - Assistant Professor of Chemistry & Chemical Biology, Cornell University

*"Protein Allostery: Evolution and Correlated Motions"*

Join us on Zoom: https://umich.zoom.us/j/99976448506

ABSTRACT: Understanding the relationship between protein sequence, structure, dynamics, and function is the ultimate goal of structural biology. For this reason, my lab studies protein allostery - a special property of macromolecules that connects molecular motion and action. In this talk, I'll present two stories. First, I'll talk about how the evolution of allosteric mechanisms and the tools of structural biology can teach us about the relationship between protein sequence and function. In the second story, I'll talk about how one can learn about correlated motions that give rise to allostery.

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Livestream / Virtual Mon, 02 Nov 2020 09:56:44 -0500 2020-11-06T12:00:00-05:00 2020-11-06T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Nozomi Ando
Biophysics Seminar Series (November 13, 2020 12:00pm) https://events.umich.edu/event/77921 77921-19941586@events.umich.edu Event Begins: Friday, November 13, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Virtual Seminar Series presents:

Dr. Nancy Forde - Department of Physics, Simon Fraser University

*“Collagen: a fascinating responsive material building block from Nature”*

Join us on Zoom: https://umich.zoom.us/j/96009492561

Abstract: Multicellular life is scaffolded by structures that maintain cells in the desired locations and organizations. Conventionally these extracellular scaffolds have been viewed as rigid, unchanging supports laid down during development and unaltered except by injury or disease. Recent scientific advances are revealing instead that these matrices are highly dynamic and respond to changes in their local microenvironment, in turn affecting cells. The collagen family of proteins has been selected via evolution as the preferred building block of these extracellular structures.

In this talk, I will introduce some of the fascinating physical properties of the unique triple-helix structure of collagen, and will highlight the results of our investigations into its mechanical properties. Our single-molecule approaches include centrifuge force microscopy, optical tweezers and atomic force microscopy, and many parallels can be drawn with the mechanics of DNA. Our work is revealing clues as to how stability is encoded within collagen’s sequence, and how collagen’s triple helix balances structural stability with responsiveness to applied force and chemical environment.

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Livestream / Virtual Wed, 04 Nov 2020 11:44:26 -0500 2020-11-13T12:00:00-05:00 2020-11-13T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Nancy Forde
Biophysics Seminar Series (November 20, 2020 12:00pm) https://events.umich.edu/event/77922 77922-20319908@events.umich.edu Event Begins: Friday, November 20, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Virtual Seminar Series presents:

Dr. Gabriele Varani - Department of Chemistry, University of Washington

*"Small drug-like molecules targeting RNA with nanomolar affinity and cellular activityon"*

Join us on Zoom: https://umich.zoom.us/j/99793210061

ABSTRACT: The ever expanding appreciation of the role of RNA in healthy and disease cellular states has created ever increasing opportunities to redress human disease by targeting RNA with small molecules. However, the chemistry of small molecules targeting RNA remains a challenge. The academic literature has been littered since the mid-1990s with reports of small molecules binding to RNA that, in most cases, did not have the pharmaceutical properties of successful drug candidates and did not bind to RNA potently nor specifically. Screening protein-directed chemical libraries allows the discovery of drug-like molecules that bind to RNA, but success rates are low, typically 1/10,000, and affinity typically in the low to mid-uM range. We have discovered RNA-binding small molecules that obey Lipinski and RO5 rules and bind to RNA potently (low to mid nM) and specifically (discriminate single nucleotide changes). These molecules target RNAs considered 'undruggable' with low nM affinity. Their size (<400 Da), absence of charge, and in vitro pharmacological properties (ADME and in vitro pharmacology) are those of favorable drug candidates. We will illustrate two examples of the application of this chemistry by reporting 10 nM ligands for HIV TAR and 100 nM ligands for pre-miR-21 with specific biochemical and cellular activity against this potent oncogene.

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Livestream / Virtual Mon, 16 Nov 2020 13:13:38 -0500 2020-11-20T12:00:00-05:00 2020-11-20T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Gabriele Varani
Biophysics Seminar Series (December 4, 2020 12:00pm) https://events.umich.edu/event/77923 77923-19941588@events.umich.edu Event Begins: Friday, December 4, 2020 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Virtual Seminar Series presents:

Dr. Oleg Igoshin - Professor of Bioengineering & BioSciences, Associate Chair of Bioengineering, Rice University

*“Understanding Trade-offs in Biological Error Correction”*

Join us on Zoom: https://umich.zoom.us/j/96475935279

Abstract: High accuracy of major biological processes relies on the ability of the participating enzymatic molecules to preferentially select the correct substrate from a pool of chemically similar substrates by activating the so-called proofreading mechanisms. While the importance of such mechanisms is widely accepted, it is still unclear how evolution has optimized the biological systems with respect to their characteristic properties. We developed a comprehensive first-passage theoretical framework that allowed us to quantitatively investigate the trade-offs between four properties of enzymatic systems namely, error, speed, noise and energy dissipation. Within this framework, we simultaneously analyzed speed and accuracy of several fundamental biological processes, including DNA replication, tRNA charging, and tRNA selection during the translation. The results indicate that contrary to typical assumptions speed-accuracy trade-off is not always observed. However, when the trade-off is present, the biological systems tend to optimize the speed rather than the accuracy of the processes, as long as the error level is tolerable. When systems function in the regime where no speed-accuracy trade-off is observed, constraints due to energy dissipation in the proofreading play a key role. Our theory demonstrates a universal Pareto front in error-dissipation trade-off and shows how naturally selected kinetic parameters position their system close to this boundary. Our findings, therefore, provide a new system-level picture of how complex biological processes are able to function so fast with a high accuracy and low dissipation.

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Livestream / Virtual Tue, 01 Dec 2020 08:40:21 -0500 2020-12-04T12:00:00-05:00 2020-12-04T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Igoshin
Complex Systems Presents: A Nobel Symposium (December 10, 2020 1:10pm) https://events.umich.edu/event/79125 79125-20209862@events.umich.edu Event Begins: Thursday, December 10, 2020 1:10pm
Location: Off Campus Location
Organized By: The Center for the Study of Complex Systems

VIRTUAL SYMPOSIUM LINK: myumi.ch/v2ZYv

Registration not required. Free and open to the public. This virtual event features UM faculty experts in each of the six prize fields. Each will present for 25 minutes and take questions for 10 minutes

1:10 - 1:15 Welcome remarks Charlie Doering CSCS Director

1:15 - 1:50 CHEMISTRY | Nils Walter Chemistry, Biophysics and Biological Chemistry LSA and Medical School

1:50 - 2:25 MEDICINE OR PHYSIOLOGY | Katherine Spindler Microbiology and Immunology Medical School

2:25 - 3:00 PHYSICS | Lydia Bieri Mathematics and Doug Richstone  Astronomy LSA

3:00 - 3:35 ECONOMICS | Tilman Börgers Economics

3:35 - 4:10 LITERATURE | Linda Gregerson Literature LSA

4:10 - 4:45 PEACE | Susan Waltz Public Policy, Gerald R Ford School of Public Policy

Information about the 2020 prizes and our speakers:

*Chemistry:*
The Nobel Prize in Chemistry 2020 was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna "for the development of a method for genome editing."

Speaker: *Nils Walter*, Francis S Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry – College of Literature, Science, and the Arts and Medical School

*Physiology or Medicine:*
The 2020 Nobel Prize in Physiology or Medicine is awarded jointly to *Harvey J. Alter, Michael Houghton* and *Charles M. Rice* “for the discovery of Hepatitis C virus”. Thanks to their discovery, highly sensitive blood tests for the virus are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the world, greatly improving global health.

Speaker: *Katherine Spindler,* Professor of Microbiology and Immunology – Michigan Medicine

*Physics:*
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2020 with one half to *Roger Penrose* “for the discovery that black hole formation is a robust prediction of the general theory of relativity" and the other half jointly to *Reinhard Genzel* and *Andrea Ghez* "for the discovery of a supermassive compact object at the centre of our galaxy".

Speaker: *Lydia Bieri*, Associate Professor of Mathematics and Director, Michigan Center for Applied & Interdisciplinary Mathematics and *Doug Richstone*, Lawrence H Aller Collegiate Professor of Astronomy – College of Literature, Science, and the Arts

*Economics:*
This year’s Laureates, *Paul Milgrom* UM-LSA Mathematics Alum! and *Robert Wilson*, have studied how auctions work. They have also used their insights to design new auction formats for goods and services that are difficult to sell in a traditional way, such as radio frequencies. Their discoveries have benefitted sellers, buyers and taxpayers around the world.

Speaker:* Tilman Börgers*, Samuel Zell Professor of the Economics of Risk – College of Literature, Science, and the Arts

*Literature:*
The Nobel Prize in Literature for 2020 is awarded to the American poet Louise Glück “for her unmistakable poetic voice that with austere beauty makes individual existence universal”.

Speaker: *Linda Gregerson*, Caroline Walker Bynum Distinguished University Professor of English Language and Literature – College of Literature, Science, and the Arts

*Peace:*
'Combatting the threat of hunger' The Norwegian Nobel Committee has decided to award the Nobel Peace Prize for 2020 to the *World Food Programme (WFP)*. The World Food Programme is the world’s largest humanitarian organization addressing hunger and promoting food security. In 2019, the WFP provided assistance to close to 100 million people in 88 countries who are victims of acute food insecurity and hunger.

The World Food Programme is the food-assistance branch of the United Nations and the world's largest humanitarian organization focused on hunger and food security. Founded in 1961, it is headquartered in Rome and has offices in 80 countries

Speaker: *Susan Waltz*, Professor of Public Policy, Gerald R Ford School of Public Policy

Read more about the details of each of the 2020 prizes here: https://www.nobelprize.org/prizes/

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Livestream / Virtual Mon, 07 Dec 2020 16:19:38 -0500 2020-12-10T13:10:00-05:00 2020-12-10T16:45:00-05:00 Off Campus Location The Center for the Study of Complex Systems Livestream / Virtual Nobel Symposium Poster
Biophysics Seminar Series (January 15, 2021 12:00pm) https://events.umich.edu/event/80417 80417-20719670@events.umich.edu Event Begins: Friday, January 15, 2021 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Virtual Seminar Series presents:

Dr. Michele Vendruscolo - Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge

*“Activity Relationship by Kinetics for Drug Discovery in Protein Misfolding Diseases”*

ABSTRACT: Protein oligomers are increasingly recognized as the most cytotoxic forms of protein aggregates. It has been very challenging, however, to target these oligomers with therapeutic compounds, because of their dynamic and transient nature. To overcome this problem, I will describe a 'structure kinetic-activity relationship' (SKAR) approach, which enables the discovery and systematic optimization of compounds that reduce the number of oligomers produced during an aggregation reaction. I will illustrate this strategy for the amyloid beta peptide, which is closely associated with Alzheimer's disease, by developing a rhodanine compound capable of dramatically reducing the production of amyloid beta oligomers. As this strategy is general, it can be applied to oligomers of any protein.

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Livestream / Virtual Wed, 06 Jan 2021 10:17:32 -0500 2021-01-15T12:00:00-05:00 2021-01-15T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Michele Vendruscolo
Biophysics Seminar Series (January 22, 2021 12:00pm) https://events.umich.edu/event/80727 80727-20777543@events.umich.edu Event Begins: Friday, January 22, 2021 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Virtual Seminar Series presents:

Dr. Katrin Heinze - Rudolf Virchow Center for Integrative and
Translational Bioimaging, Universität Würzburg

*“Boosting high-resolution fluorescence by tunable nano-coatings"*

ABSTRACT: The “Resolution Revolution" in fluorescence microscopy over the last decades has given rise to a variety of techniques that allow imaging beyond the diffraction limit with resolution up to the nanometer range. One particularly powerful technique is direct stochastic optical
reconstruction microscopy (dSTORM), a widely-used type of single molecule localization microscopy (SMLM), which is based on the temporal separation of the emission of individual fluorophores
and subsequent localization analysis. This eventually allows to reconstruct a super-resolved image revealing details down to typically 20 nm in a cellular setting. The key point here is the achievable localization precision, which mainly depends on the image contrast generated by the individual fluorophore’s emission. We found that reflective metal-dielectric nano-coatings represent a tunable nanomirror that can do both quenching and boosting fluorescence for high-contrast imaging on the nanoscale. Such mirror-enhanced fluorescence is very different from other surface effects based on total internal reflection microscopy or optoplasmonics. While surface-plasmon supported fluorescence methods provide much higher enhancement factors, mirror-enhanced approaches are more versatile and thus highly suitable for modern bio-imaging. The resolution improvement achieved with such mirror-enhanced STORM (meSTORM) is both spectrally and spatially tunable and thus allows for dual-color approaches on the one hand, and selectively highlighting region above the cover glass on the other hand. Even if the resulting resolution boost is based on a near-field effect and thus restricted to imaging near surfaces, a large variety of membrane fluorescence approaches even beyond SMLM benefit. Thus, live-cell
Fluorescence Correlation Spectroscopy and Fluorescence Resonance Energy Transfer are as well perfect candidates to be pushed to the next level.

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Livestream / Virtual Wed, 13 Jan 2021 15:37:36 -0500 2021-01-22T12:00:00-05:00 2021-01-22T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Katrin Heinze
Biophysics Seminar Series (January 29, 2021 12:00pm) https://events.umich.edu/event/81244 81244-20877916@events.umich.edu Event Begins: Friday, January 29, 2021 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

*“Ultrafast 2D IR Spectroscopy of Membrane Peptide Systems”*

Plasma membranes are the main liaisons between the intercellular and extracellular environment, playing a critical role in numerous biological processes. Recent research has challenged the long-standing “fluid mosaic model,” representing membranes as densely packed, heterogeneous environments. Within these complex membranes are transmembrane proteins which comprise up to 50% of the membrane mass, and are themselves diverse in sequence, structure, and function. Combining two-dimensional infrared spectroscopy (2D IR) and molecular dynamics simulations (MD), we have explored membrane complexity from two perspectives: first, we address the sequence heterogeneity in transmembrane peptides; and second, we explore the effect this crowded environment has on the lipids themselves and the implications this has on future membrane studies.

Site-specific 2D IR has been used to directly study localized hydration effects in a lipid membrane upon insertion of pH (Low) Insertion Peptide (pHLIP), a model membrane peptide. Semi-quantitative results indicate enhanced water penetration in the membrane core concurrent with peptide insertion, suggesting the abundance of hydrophilic residues in the pHLIP sequence drives membrane hydration. Further, crowding experiments have probed ultrafast dynamics at the lipid-water interface of model membranes as a function of transmembrane peptide concentration, revealing a non-monotonic dependence on peptide concentration linked to interfacial water structure.

Zoom link: https://umich.zoom.us/j/99088330811

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Livestream / Virtual Tue, 26 Jan 2021 10:51:35 -0500 2021-01-29T12:00:00-05:00 2021-01-29T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Jennifer Flanagan
Biophysics Seminar Series (March 12, 2021 12:00pm) https://events.umich.edu/event/82542 82542-21116092@events.umich.edu Event Begins: Friday, March 12, 2021 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The Biophysics Seminar Series Presents:

Dr. Pratyush Tiwary - Department of Chemistry & Biochemistry and Institute for Physical Science & Technology, University of Maryland

*“Can artificial intelligence help understand and predict biomolecular dynamics?”*

ABSTRACT: The ability to rapidly learn from high-dimensional data to make reliable predictions about the future of a given system is crucial in many contexts. This could be a fly avoiding predators, or the retina processing terabytes of data almost instantaneously to guide complex human actions. In this talk we draw parallels between such tasks, and the efficient sampling of complex molecules with hundreds of thousands of atoms. Such sampling is critical for predictive computer simulations in condensed matter physics and biophysics, including but not limited to problems such as crystal nucleation, protein loop movement and drug unbinding. For this we use the Predictive Information Bottleneck (PIB) and long short-term memory (LSTM) frameworks from artificial intelligence (AI), and re-formulate them for the sampling of biomolecular structure and dynamics, especially when plagued with rare events. We demonstrate the methods on different test-pieces, where we calculate the dissociation pathway and timescales much longer than milliseconds. These include ligand dissociation from the protein lysozyme, protein kinases and and from flexible RNA. We will also discuss some generic challenges and proposed solutions regarding reliability, interpretability and extrapolative powers of AI when used in molecular simulations, drawing mutually beneficial connections between the at first glance disconnected fields of theoretical chemistry and AI.

*Join us on zoom: https://umich.zoom.us/j/92734220731*

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Livestream / Virtual Thu, 25 Feb 2021 14:10:27 -0500 2021-03-12T12:00:00-05:00 2021-03-12T13:00:00-05:00 Off Campus Location LSA Biophysics Livestream / Virtual Dr. Pratyush Tiwary
“Ions and proteins: the essential partners that fold RNA and DNA” (April 9, 2021 12:00pm) https://events.umich.edu/event/81780 81780-20959267@events.umich.edu Event Begins: Friday, April 9, 2021 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

Abstract: The nucleic acids, RNA and DNA, play versatile and critically important roles in biology. The information storage capacity of DNA has long been recognized, and awareness of RNA’s prominence in biology continues to grow. Because both RNA and DNA carry large negative charge, interaction with oppositely charged partners is required for folding and function. Despite the important roles of these partners, little is known about how they structure, or interact with nucleic acids. We design experiments to reveal the role of partners, ranging from ions through proteins, in systems ranging from single stranded DNA or RNA through large assemblies, like viruses. Simulation and computation are important components of our work, and often offer surprising insight into our results.

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Livestream / Virtual Fri, 02 Apr 2021 11:29:54 -0400 2021-04-09T12:00:00-04:00 2021-04-09T13:00:00-04:00 Off Campus Location LSA Biophysics Livestream / Virtual Lois Pollak
TBA (July 27, 2021 1:00pm) https://events.umich.edu/event/84773 84773-21624929@events.umich.edu Event Begins: Tuesday, July 27, 2021 1:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

TBA

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Workshop / Seminar Tue, 27 Jul 2021 13:41:28 -0400 2021-07-27T13:00:00-04:00 2021-07-27T14:00:00-04:00 Off Campus Location LSA Biophysics Workshop / Seminar
U-M Physics REU Symposium (August 12, 2021 10:00am) https://events.umich.edu/event/84836 84836-21625109@events.umich.edu Event Begins: Thursday, August 12, 2021 10:00am
Location: West Hall
Organized By: Department of Physics

Undergraduate students who have been performing research over the summer will present their findings at the REU symposium. Presenters will include both visiting REU students and students from the Department of Physics.

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Conference / Symposium Fri, 30 Jul 2021 12:20:12 -0400 2021-08-12T10:00:00-04:00 2021-08-12T17:00:00-04:00 West Hall Department of Physics Conference / Symposium REU Research Photo
Functional roles of phase separation at the plasma membrane (September 10, 2021 12:00pm) https://events.umich.edu/event/84683 84683-21626063@events.umich.edu Event Begins: Friday, September 10, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Research in the Veatch lab over the last decade has used conventional and super-resolution fluorescence localization microscopy to interrogate the structure and function of phase-related heterogeneity in plasma membranes. This presentation will highlight recent advances from the lab, including our work to demonstrate that membrane phase separation contributes to the organization, dynamics, and signaling activity of proteins at B cell receptor clusters. I will also discuss our recent theoretical work examining emergent properties of polymer rich droplets at heterogeneous membranes, making predictions for how liquid-liquid phase separation in the cytoplasm couples to the distinct phase transition at the plasma membrane.

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Workshop / Seminar Tue, 24 Aug 2021 13:14:20 -0400 2021-09-10T12:00:00-04:00 2021-09-10T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Sarah Veatch
Analyzing Anomalous Diffusion in Single-Molecule Tracks with Nonparametric Bayesian Inference and Deep Learning (September 17, 2021 12:00pm) https://events.umich.edu/event/86157 86157-21631748@events.umich.edu Event Begins: Friday, September 17, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Single-particle tracking (SPT) enables the investigation of biomolecular dynamics at a high temporal and spatial resolution in living cells, and the analysis of these SPT datasets can reveal biochemical interactions and mechanisms. We have developed a new SPT analysis framework, NOBIAS, which applies nonparametric Bayesian statistics and deep learning approaches to thoroughly analyze SPT datasets. We utilize a Hierarchical Dirichlet process Hidden Markov Model (HDP-HMM) to infer the number of diffusive states and the associated dynamics, populations and step labels for each diffusive state, then we apply a Recurrent Neural Network (RNN) to classify the diffusion type of each diffusive state. We further validate the performance of NOBIAS with simulated tracks and the quantify diffusion of single outer-membrane proteins in Bacteroides thetaiotaomicron.

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Workshop / Seminar Wed, 01 Sep 2021 13:42:06 -0400 2021-09-17T12:00:00-04:00 2021-09-17T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
Investigation of RNA 3D structure and small molecule interactions by a multidisciplinary approach (September 17, 2021 12:00pm) https://events.umich.edu/event/84766 84766-21624922@events.umich.edu Event Begins: Friday, September 17, 2021 12:00pm
Location:
Organized By: LSA Biophysics

Elizabeth D Tidwell1,2; Anna Anders3; Varun Gadkari3; Brandon T Ruotolo3, Aaron T Frank1, and Markos Koutmos1,2,3

1 University of Michigan Department of Biophysics, 2 University of Michigan Chemical Biology Interface Training Program 5T32GM132046-02, 3 University of Michigan Department of Chemistry.

Structured RNAs regulate many key processes in pathogens like bacteria and viruses; yet RNA remains under-explored as a drug target. Visualizing the structures and structural transitions of RNAs are important for RNA therapeutic development; however, there is limited structural data, dynamic information, and incomplete understanding of RNA interactions with small molecules (SM). We are developing a pipeline that combines automated and high-throughput analytical, structural, and synthetic biology tools with molecular modeling and machine learning for rapid and large-scale exploration of RNA structure and RNA:SM interactions. We selected riboswitches to train our method—beginning with the flavin mononucleotide riboswitch (FMN-RS) due to the availability of high-resolution structures with and without its cognate FMN substrate and other previously identified ligands. We performed rigid body docking simulations to identify and rank structurally distinct SM on their potential to recapitulate the ligand interaction between FMN and FMN-RS. Then, we optimized and altered two commonly used in vitro screening methods for protein:SM interactions—ion mobility mass spectrometry (IM-MS) and biolayer interferometry (BLI)—for use with RNA. We have successfully optimized RNA sample preparation and data collection for IM-MS using FMN-RS and mitochondrial tRNA leucine. Using collision induced unfolding, we have determined the unfolding states of FMN-RS in the presence and absence of ligand. Additionally, we have successfully used the Octet Red BLI system to measure the FMN-RS interaction with SM. We obtained kinetic binding information with identified ligands of FMN-RS and screened a subset of the predicted SM from our simulations. The results from each in vitro experiment will be used to alter and improve the search criteria for the simulations and illuminate properties of the SM:RNA interactions. Our interdisciplinary methodology will be further optimized to streamline identification of conformationally selective RNA SM binders and potentially improve drug discovery.

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Workshop / Seminar Wed, 08 Sep 2021 15:26:35 -0400 2021-09-17T12:00:00-04:00 2021-09-17T13:00:00-04:00 LSA Biophysics Workshop / Seminar
Balancing spatial heterogeneity and migration to slow the evolution of resistance in a bacterial pathogen (September 24, 2021 12:00pm) https://events.umich.edu/event/86117 86117-21631587@events.umich.edu Event Begins: Friday, September 24, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Spatial heterogeneity can dramatically impact evolution in bacterial communities, raising the question of whether spatial profiles of drug concentration can be tuned to slow the emergence of antibiotic resistance. In this work, we combine lab evolution experiments in spatially connected, computer-controlled chemostats with mathematical models to investigate resistance evolution in E. faecalis, an opportunistic bacterial pathogen. We find that both the rate of adaptation to doxycycline, a protein-synthesis inhibiting antibiotic, and the associated cost of resistance in the associated mutants depends strongly on drug concentration in spatially uniform populations. Interestingly, when spatially separated subpopulations are exposed to different concentrations of drug, adaptation can be dramatically slowed by tuning the rate of migration between habitats, leading to selection for phenotypically distinct resistant mutants. Our results highlight the rich evolutionary dynamics of adaptation in spatially connected habitats and indicate that resistance evolution can be slowed by balancing evolutionary trade-offs of migration and heterogeneity.

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Workshop / Seminar Wed, 01 Sep 2021 11:40:56 -0400 2021-09-24T12:00:00-04:00 2021-09-24T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
Investigation of structural switch that regulates pre-miR-92a processing by NMR (September 24, 2021 12:00pm) https://events.umich.edu/event/84767 84767-21624923@events.umich.edu Event Begins: Friday, September 24, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

MicroRNAs (miRNAs) regulate gene expression in a variety of biological pathways such as development and tumorigenesis. miRNAs are initially expressed as a long primary transcripts (pri-miRNA) which are processed to yield pre-miRNAs and ultimately mature miRNAs. The miR-17-92a cluster, also known as ‘oncomiR-1’ is a polycistronic pri-miRNA that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. OncomiR-1 includes six constitute miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. However, the structural mechanism that regulate the differential processing still remain unclear.
NMR is a key technique that has significantly advanced our understanding of RNA structure and dynamics. In vitro processing assays indicate that pre-miR-92a processing is inhibited relative to other miRs within oncomiR-1. We are interested in uncovering the structural basis for the differential processing by NMR. NPSL2 has been identified as an inhibitor of pre-miR-92a processing. Therefore, in this work we determined the solution structure of NPSL2. Our data suggest that NPSL2 is dynamic, and we hypothesize that the dynamics are linked to regulation of processing. Our ongoing efforts will investigate the mechanism of the structural switch that promotes premiR-92a processing in the context of the full-length oncomiR-1 RNA.

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Workshop / Seminar Wed, 01 Sep 2021 11:32:04 -0400 2021-09-24T12:00:00-04:00 2021-09-24T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab