Happening @ Michigan https://events.umich.edu/list/rss RSS Feed for Happening @ Michigan Events at the University of Michigan. 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
Structural origin of the mechanics and fracture properties of articular cartilage (October 1, 2021 12:00pm) https://events.umich.edu/event/84685 84685-21624425@events.umich.edu Event Begins: Friday, October 1, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Articular cartilage (AC) is a soft tissue that provides a smooth cushion and distributes the mechanical load in joints. As a material, AC is remarkable. It is only a few millimeters thick, can bear up to ten times our body weight over 100-200 million loading cycles despite minimal regenerative capacity, and still avoids fracturing. The simultaneous strength, fracture resistance, and longevity of native AC remain unmatched in synthetic materials. Such properties are desperately needed for tissue engineering, tissue repair, and even soft robotics applications. I will discuss the structural origins of and microscopic mechanisms leading to AC’s exceptional mechanical properties using the framework of rigidity percolation theory and compare our predictions with experiments. Our results provide an understanding of the tissue depth-dependent mechanical properties and how tissue mechanics changes in response to changes in tissue composition during diseases such as osteoarthritis. This framework also offers insights into how structure, composition, and constitutive mechanical properties can be tuned to resist and blunt cracks in AC and cartilage-inspired soft materials. The flexibility in resulting material properties and ease of implementation can be harnessed to fabricate artificial tissue constructs with tunable mechanics. I will discuss results that are an important step towards achieving this future.

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Workshop / Seminar Thu, 30 Sep 2021 10:33:41 -0400 2021-10-01T12:00:00-04:00 2021-10-01T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
From molecules to development: how biological clocks function and coordinate (October 8, 2021 12:00pm) https://events.umich.edu/event/84686 84686-21624426@events.umich.edu Event Begins: Friday, October 8, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Organisms from bacteria to humans employ complex biochemical or genetic oscillatory networks, termed biological clocks, to drive a wide variety of essential cellular and developmental processes for robust timing. Despite their complexity and diversity, these clocks seem to share some core architectures that are highly conserved from species to species, suggesting an essential role of network structures underlying clock functioning.

The Yang lab, bridging biophysics and systems & synthetic biology, has integrated modeling with experiments in minimal systems to elucidate universal physical mechanisms underlying the complex processes. In this talk, I will focus on our recent efforts in answering several fundamental questions regarding the design and behaviors of cell cycles and embryonic developmental patterns. Computationally, we have identified network motifs, notably incoherent inputs, that universally enhance systems' robust performance. Experimentally, we developed a unique synthetic-cell system to analyze circuits and functions of robustness and tunability in cell-sized microfluidic droplets. We also explore the role of energy and mechanical and biochemical signaling in spatiotemporal patterns.

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Workshop / Seminar Thu, 30 Sep 2021 10:32:09 -0400 2021-10-08T12:00:00-04:00 2021-10-08T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
Relating Structure and Function in Actin (October 15, 2021 12:00pm) https://events.umich.edu/event/84768 84768-21624924@events.umich.edu Event Begins: Friday, October 15, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Actin is one of the most abundant intracellular proteins and it is highly conserved across all eukaryotes. The primary functional form of actin is the filament, formed by the polymerization of actin monomers. This polymerization process is exquisitely controlled through a host of actin-binding proteins, but since actin is an ATPase, it is also a function of the bound nucleotide. Much of our understanding of actin comes from experiments using animal cells, but even though the protein sequence is strongly conserved, the function and dynamics of actin in yeast, or more primitive systems, show some interesting differences. In this talk I will present results from a combination of simulations and mathematical modeling that provide new insight into the sequence-structure-function relationship in this important protein.

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Workshop / Seminar Wed, 06 Oct 2021 13:19:22 -0400 2021-10-15T12:00:00-04:00 2021-10-15T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
TBA (October 22, 2021 12:00pm) https://events.umich.edu/event/84769 84769-21624925@events.umich.edu Event Begins: Friday, October 22, 2021 12:00pm
Location:
Organized By: LSA Biophysics

TBA

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Workshop / Seminar Tue, 27 Jul 2021 13:25:49 -0400 2021-10-22T12:00:00-04:00 2021-10-22T13:00:00-04:00 LSA Biophysics Workshop / Seminar
Division of Labor and Mechanism of Translocation in a Ring ATPase (October 29, 2021 12:00pm) https://events.umich.edu/event/84687 84687-21624427@events.umich.edu Event Begins: Friday, October 29, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Many transport processes in the cell are performed by a diverse but structurally and functionally related family of proteins. These proteins, which belong to the ASCE (Additional Strand, Conserved E) superfamily of ATPases, often form mutimeric rings. Despite their importance, a number of fundamental questions remain as to the coordination of the various subunits in these rings. Bacteriophage phi29 packages its 6.6 mm long double-stranded DNA using a pentameric ring nano motor Using optical tweezers, we find that this motor can work against loads of up to ~55 picoNewtons on average, making it one of the strongest molecular motors ever reported. Interestingly, the packaging rate decreases as the prohead fills, indicating that an internal pressure builds up due to DNA compression attaining the value of ~3 MegaPascals at the end of packaging, a pressure that is used as part of the mechanism of DNA injection in the next infection cycle. We have used high-resolution optical tweezers to show that the motor packages the DNA in alternating phases of dwells and bursts. During the dwell the motor exchanges nucleotide, whereas during the burst, the motor packages 10 bps of DNA per cycle. We have also characterized the steps and intersubunit coordination of this ATPase. By using non-hydrolyzable ATP analogs and stabilizers of the ADP bound to the motor, we establish where DNA binding, hydrolysis, and phosphate and ADP release occur relative to translocation during the motor’s cycle. Surprisingly, a division of labor exists among the subunits: while only 4 of the subunits translocate DNA, all 5 bind and hydrolyze ATP, suggesting that the fifth subunit fulfills a regulatory function. Furthermore, we show that the motor not only can generate force but also torque. We characterize the role played by the special subunit in this process and identify the symmetry-breaking mechanism in the motor. Finally, we use dsRNA, and RNA/DNA hybrids to establish what factor determines the size of the motor burst, which together with recent structural data, allows us to propose a novel mechanism of translocation for this motor.

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Workshop / Seminar Mon, 18 Oct 2021 09:28:00 -0400 2021-10-29T12:00:00-04:00 2021-10-29T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
RNA Diffusion Behavior Changes Under Hyperosmotic Phase Separation & Coupled Oscillators in Developmental Patterning and Growth (November 5, 2021 12:00pm) https://events.umich.edu/event/84770 84770-21624926@events.umich.edu Event Begins: Friday, November 5, 2021 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Proteins and RNAs can form functional biological condensates, also known as me braneless organelles, via liquid-liquid phase separation (LLPS). The partitioning of different proteins and RNAs between the dilute phase and the condensed phase provides delicate regulation over their functions, from promoting biochemical reactions and specific intermolecular interactions, to sequestering key molecules from downstream processing or signaling. Hyperosmotic phase separation (HOPS) is a recently discovered LLPS triggered by the hyperosmotic compression of cell volume. A majority of homo-multimeric proteins are shown to undergo HOPS in several cell types, including kidney cells that experience osmolarity fluctuations daily. Moreover, HOPS is much faster than most cellular LLPS processes (within ~10 s versus over minutes to hours), and thus HOPS condensates could be first responders sensing cell volume change and priming other stress responses. However, it was unclear whether RNAs contribute to HOPS and how HOPS impacts the diffusion behaviors and functions of different RNAs. Here, I used both fixed-cell super-resolution imaging and live-cell single molecule RNA tracking to quantify the interaction of mRNAs, lncRNAs, and miRNAs with HOPS condensates, and measure the change in their diffusion behaviors in the presence of HOPS. The preliminary results suggest that different RNAs have distinctive partitioning behaviors among HOPS condensates, and long-range active transport of RNAs are diminished under hyperosmotic conditions, presumably due to the compartmentalization by HOPS condensates.
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Coordinated regulation of cell proliferation and differentiation is fundamental to the growth and patterning of multicellular structures. To understand how growth and patterning are coupled during vertebrate development, we designed both in-vivo and in-vitro systems to study the interactions between the cell cycle and the segmentation clock across different scales. We use a 3D zebrafish embryonic tissue model to demonstrate that the phase dynamics of the cell cycle and segmentation clock are spatially dependent. To further study the spatiotemporal dynamics of the two clocks, we designed a microfluidic oscillator device to show that fine tuning kinetic parameters allows control of morphogen gradients, laying preliminary work towards constructing an artificial segmentation clock

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Workshop / Seminar Mon, 01 Nov 2021 13:44:12 -0400 2021-11-05T12:00:00-04:00 2021-11-05T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
Genome Organization through Phase Separation: Random yet Precise (November 12, 2021 12:00pm) https://events.umich.edu/event/84688 84688-21624428@events.umich.edu Event Begins: Friday, November 12, 2021 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The three-dimensional genome organization plays an essential role in all DNA-templated processes, including gene transcription, gene regulation, DNA replication, etc. Coarse-grained models parameterized to reproduce experimental data via the maximum entropy optimization algorithm serve as effective means to study genome organization at various length scales. They have provided insight into the principles of whole-genome organization and enabled de novo predictions of chromosome structures from epigenetic modifications. In addition, they provided insight into the critical role of the chromatin network in stabilizing multiple liquid droplets. Applications of these models at a near-atomic resolution further revealed physicochemical interactions that drive the phase separation of disordered proteins and dictate chromatin stability in situ.

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Workshop / Seminar Mon, 01 Nov 2021 13:53:57 -0400 2021-11-12T12:00:00-05:00 2021-11-12T13:00:00-05:00 Off Campus Location LSA Biophysics Workshop / Seminar
NMR and bioinformatic approaches to understanding how intrinsically disordered proteins modulate biomolecular condensates (December 3, 2021 12:00pm) https://events.umich.edu/event/84690 84690-21624430@events.umich.edu Event Begins: Friday, December 3, 2021 12:00pm
Location:
Organized By: LSA Biophysics

The role of biomolecular condensates in regulating biological function and the importance of dynamic interactions involving intrinsically disordered protein regions (IDRs) in their assembly are increasingly appreciated. Elucidating the critical interactions that govern condensation via phase separation is challenging due to the lack of applicability of standard structural biological tools to study these highly dynamic large-scale associated states and the lack of applicability of standard bioinformatic tools to study low complexity sequences that are not easily alignable. Using the C-terminal IDR (607 to 709) of CAPRIN1, an RNA-binding protein found in cytoplasmic biomolecular condensates, we have applied NMR methods developed by Lewis Kay to obtain site-specific information on key interactions that control phase separation and on the modulation of phase separation by post-translational modifications and ATP. We have developed, with Alan Moses, a bioinformatics approach for IDRs that does not require alignments and that identifies conserved molecular features (such as biophysical properties), termed “evolutionary signatures.” Groups of IDRs with similar evolutionary signatures are highly enriched for functional annotations and phenotypes, including clusters that are strongly linked to particular biomolecular condensates. We can utilize a feature-based approach to understand the types of interactions within specific condensates and how disease mutations that perturb conserved features may drive pathology. We also developed a new phase separation predictive tool based on sequence statistics for different physicochemical interactions within the folded protein database that provides insights into the key interactions underlying condensates. These experimental and computational methods should enable deeper understanding of how IDRs contribute to biological regulation via biomolecular condensates.

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Workshop / Seminar Fri, 05 Nov 2021 14:11:26 -0400 2021-12-03T12:00:00-05:00 2021-12-03T13:00:00-05:00 LSA Biophysics Workshop / Seminar
TBA (December 10, 2021 12:00pm) https://events.umich.edu/event/84691 84691-21624431@events.umich.edu Event Begins: Friday, December 10, 2021 12:00pm
Location:
Organized By: LSA Biophysics

TBA

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Workshop / Seminar Wed, 21 Jul 2021 14:51:46 -0400 2021-12-10T12:00:00-05:00 2021-12-10T13:00:00-05:00 LSA Biophysics Workshop / Seminar
Hybrid self-assembled nanomaterials from proteins, peptides, and DNA (January 7, 2022 12:00pm) https://events.umich.edu/event/84772 84772-21624927@events.umich.edu Event Begins: Friday, January 7, 2022 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

The ability to design materials that mimic the complexity and functionality of biological systems is a long standing goal of nanotechnology, with applications in medicine, energy, and fundamental science. Biological molecules such as proteins, peptides, and DNA possess a rich palette of self-assembly motifs and chemical functional diversity, and are attractive building blocks for the synthesis of such nanomaterials. In this talk, we will describe research in creating hybrid materials that incorporate proteins and peptides with DNA nanotechnology to create cages, nanofibers, and 3D crystals with a high degree of programmability and nanoscale resolution. Key to these endeavors will be (bio)molecular design, organic chemistry for linking components in a site-specific fashion, and the tuning of multiple self-assembly "modes" to create hybrid structures. Although the talk will focus on the fundamental chemistry and self-assembly of these systems, we will also discuss potential applications in areas such as targeted cargo delivery, biomaterials for regenerative medicine, biophysical devices, and synthesis of virus- and antibody-mimetic nanostructures.

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Workshop / Seminar Mon, 03 Jan 2022 09:09:21 -0500 2022-01-07T12:00:00-05:00 2022-01-07T13:00:00-05:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
Biophysics in industry: Real-time measurement and manipulation of single-molecule interactions: from DNA-binding proteins to biomolecular condensates (January 14, 2022 12:00pm) https://events.umich.edu/event/90313 90313-21670330@events.umich.edu Event Begins: Friday, January 14, 2022 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

Biological processes emerge from mechanisms at the molecular scale. While biophysical techniques (e.g., X-ray crystallography, cryoEM) with bulk biochemical assays (e.g., enzymatic reactions, fluorescent reporters) have helped to better understand emergent structure-function relationships, the complete picture of molecular-scale mechanisms is often missed. In addition, the existing techniques often do not provide tools to observe and manipulate a biological system simultaneously and understand mechanisms from the molecular to the cellular level. In this talk, I will introduce a single-molecule tool, the C-Trap, which enables users to observe and manipulate biological systems in real-time. This technology combines two Nobel prize-winning ideas (optical tweezers and super-resolution STED microscopy), integrated with easy-to-use microfluidics, that allows users to perform single-molecule studies on a broad range of biological systems. I will present some case studies to highlight the role of C-trap in looking at DNA/RNA-proteins interactions, proteins/RNA-structure dynamics, and nucleic acid/protein condensates. The presented case studies and workflows serve as a framework for measuring and visualizing complex and dynamic biological systems, that would be extremely challenging to study using conventional biophysical techniques.

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Workshop / Seminar Fri, 07 Jan 2022 14:29:24 -0500 2022-01-14T12:00:00-05:00 2022-01-14T13:00:00-05:00 Off Campus Location LSA Biophysics Workshop / Seminar
TBA (January 21, 2022 12:00pm) https://events.umich.edu/event/90314 90314-21670331@events.umich.edu Event Begins: Friday, January 21, 2022 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

TBA

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Workshop / Seminar Mon, 03 Jan 2022 09:18:32 -0500 2022-01-21T12:00:00-05:00 2022-01-21T13:00:00-05:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
Noncoding RNA structure and recognition in stress response and immunity (January 28, 2022 12:00pm) https://events.umich.edu/event/84689 84689-21624429@events.umich.edu Event Begins: Friday, January 28, 2022 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

The goal of our research is to gain a detailed structural and mechanistic understanding of cellular and viral noncoding RNAs (ncRNAs). Our recent work has focused on investigating how two archetypes of ncRNAs — the tRNA and the double-stranded RNA (dsRNA), as well as RNAs that mimic them, mediate cellular responses to stress, regulate HIV-1 replication, and modulate host innate immunity.

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Workshop / Seminar Wed, 12 Jan 2022 13:30:19 -0500 2022-01-28T12:00:00-05:00 2022-01-28T13:00:00-05:00 Off Campus Location LSA Biophysics Workshop / Seminar
TBA (February 11, 2022 12:00pm) https://events.umich.edu/event/90315 90315-21670332@events.umich.edu Event Begins: Friday, February 11, 2022 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

TBA

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Workshop / Seminar Mon, 03 Jan 2022 09:17:22 -0500 2022-02-11T12:00:00-05:00 2022-02-11T13:00:00-05:00 Off Campus Location LSA Biophysics Workshop / Seminar
Structural biology in-situ: Human nuclear pore complex (February 25, 2022 12:00pm) https://events.umich.edu/event/92630 92630-21693810@events.umich.edu Event Begins: Friday, February 25, 2022 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Nuclear pore complex (NPCs) is the largest non-polymeric protein complex in the cell. It mediates nucleocytoplasmic transport. The intricate 120 MDa architecture remains incompletely understood. We combine AI-based structure prediction with in situ and in cellulo cryo-electron tomography and integrative modeling to report near complete model of human NPC scaffold. We show that linker Nups spatially organize the scaffold within and across subcomplexes to establish the higher-order structure. This work exemplifies how AI-based modeling can be integrated with in situ structural biology to understand subcellular architecture across spatial organization levels.

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Workshop / Seminar Mon, 21 Feb 2022 13:49:22 -0500 2022-02-25T12:00:00-05:00 2022-02-25T13:00:00-05:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
New generation of neurophotonics for multiscale access of mammalian brain (March 11, 2022 12:00pm) https://events.umich.edu/event/93013 93013-21699104@events.umich.edu Event Begins: Friday, March 11, 2022 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Human brain as the center of the nervous system controls our physiology, consciousness, and behavior. The function of the brain relies on the interactions of tens of billions of neurons through tens of trillions of synapses. Gaining precise knowledge of neural circuits relies on innovative and transformative tools for quantitative measurement of cellular dynamics and signaling in the live brain. Our lab works at the interface of optical engineering, device fabrication, image processing, and neuroscience to deliver enabling tools for neuroscience research. Specifically, we are working on three frontiers. First, the major challenge of cellular resolution function recording is the superficial access depth. Current methods are limited to ~ 1 mm depth, insufficient to access deep brain regions. We have developed Clear Optically Matched Panoramic Access Channel Technique (COMPACT) for deep-brain large-scale neurophotonic interface. I will present the results of applying COMPACT for deep-brain calcium imaging. Second, high-performance glutamate sensors and voltage indicators are on the horizon. Seeing information flow at millisecond time scale with subcellular resolution among neural circuits in the live mammalian brain is about to become a reality. However, currently available imaging tools are insufficient to keep up with the sensor response. We have developed an optical gearbox that can convert existing scopes for such high-speed measurement. I will present the results of in vivo kHz imaging. Third, cellular resolution recording has been limited to animal models. In comparison, fMRI and ultrasound can be applied to human brain. Can we leverage the advance of cellular resolution recording to address the key challenges of human brain measurement modalities? I will discuss the latest progress on the multimodal imaging of mammalian brain.

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Workshop / Seminar Fri, 04 Mar 2022 12:57:07 -0500 2022-03-11T12:00:00-05:00 2022-03-11T13:30:00-05:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab
CSCS Hybrid Seminar: The role of non-conservative interactions in non-equilibrium stochastic systems (March 22, 2022 11:30am) https://events.umich.edu/event/93138 93138-21700936@events.umich.edu Event Begins: Tuesday, March 22, 2022 11:30am
Location: Weiser Hall
Organized By: The Center for the Study of Complex Systems

HYBRID SEMINAR
https://umich.zoom.us/j/96616169868 | Weiser Hall Room 747
Password: CSCS (all caps)

Abstract: The complex world surrounding us, including all living matter and various artificial complex systems, mostly operates far from thermal equilibrium. A major goal of modern statistical physics and thermodynamics is to unravel the fundamental principles that govern the individual dynamics and collective behavior of such nonequilibrium systems, like the swarming of fish or flocking of birds. A novel key concept to describe and classify nonequilibrium systems is the stochastic entropy production, which explicitly quantifies the breaking of time-reversal symmetry. However, so far, little attention has been paid to the implications of non-conservative interactions, such as time-delayed (i.e., retarded) or non-reciprocal interactions, which cannot be represented by Hamiltonians contrasting all interactions traditionally considered in statistical physics. Non-conservative interactions indeed emerge commonly in biological, chemical and feedback systems, and are widespread in engineering and machine learning. In this talk, I will use simple time- and space-continuous models to discuss technical challenges and unexpected physical phenomena induced by non-reciprocity [1,2] and time delay [3,4].

[1] Loos and Klapp, NJP 22, 123051 (2020)
[2] Loos, Hermann, and Klapp, Entropy 23, 696 (2021)
[3] Loos and Klapp, Sci. Rep. 9, 2491 (2019)
[4] Holubec, Geiss, Loos, Kroy, and Cichos, PRL 127, 258001 (2021)

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Workshop / Seminar Tue, 08 Mar 2022 15:15:04 -0500 2022-03-22T11:30:00-04:00 2022-03-22T13:00:00-04:00 Weiser Hall The Center for the Study of Complex Systems Workshop / Seminar Sarah Loos
Jen Nwankwo (March 25, 2022 12:00pm) https://events.umich.edu/event/93014 93014-21699105@events.umich.edu Event Begins: Friday, March 25, 2022 12:00pm
Location: Off Campus Location
Organized By: LSA Biophysics

Interview with Jen Nwankwo

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Workshop / Seminar Fri, 04 Mar 2022 12:58:32 -0500 2022-03-25T12:00:00-04:00 2022-03-25T13:00:00-04:00 Off Campus Location LSA Biophysics Workshop / Seminar
Chaperoning Protein Folding with RNA, and Fun with Foldit (April 8, 2022 12:00pm) https://events.umich.edu/event/94317 94317-21733895@events.umich.edu Event Begins: Friday, April 8, 2022 12:00pm
Location: Chemistry Dow Lab
Organized By: LSA Biophysics

Maintaining the folding health of the proteome is a critical cellular task. It has recently become appreciated that RNAs and RNA:protein complexes play important roles in maintenance of proteomic health. Here, we investigate the role of RNAs in direct modulation of protein aggregation and folding. To begin, an in vitro screen identified that G-quadruplexes are highly efficient general molecular chaperones. Testing these G-quadruplexes in E. coli demonstrated that these RNAs improve the protein folding environment in the cell. Protein folding experiments showed that some G-quadruplexes directly accelerate protein folding. In-cell experiments then found that this acceleration of protein folding drives better quality protein folding in E. coli. Finally, fast protein:RNA oligomerization was discovered for several G-quadruplexes, providing a biophysical explanation for the outsized role of G-quadruplexes in protein aggregation diseases such as Alzheimer’s Disease and ALS. Together, these studies provide a striking example of how RNA structure impacts protein folding and misfolding disease. We will additionally discuss the use of citizen science both to improve structural biology research and biochemistry education using the biochemistry video game Foldit.

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Workshop / Seminar Mon, 04 Apr 2022 08:56:09 -0400 2022-04-08T12:00:00-04:00 2022-04-08T13:00:00-04:00 Chemistry Dow Lab LSA Biophysics Workshop / Seminar Chemistry Dow Lab