Biophysics Seminar

semester, 2016


Wednesday, January 20th 2016
10:10 am:
Subject: to be announced.

Wednesday, January 27th 2016
10:10 am:
Biophysics Seminar in 120 PAN
Speaker: Hermann Riecke, Northwestern
Subject: Neuronal Networks in Visual and Olfactory Sensory Processing

One of the essential tasks of the brain is is to obtain survival-relevant information about the world through its various senses. I will discuss some of our computational modeling results of aspects of the visual and the olfactory system. Through detailed biophysical modeling of a certain neuron type of the retina we have revealed the origin of oscillations that emerge in the process of retinal degeneration and may hinder the success of retinal prostheses. In the olfactory system we have developed an adaptive network model for the persistent restructuring of the olfactory network, which arises from the turn-over of a whole neuronal population. The resulting network structure is controlled by higher brain areas, which determine the survival of specific, newly born neurons. Our model suggests that this allows even very early olfactory processing to be modified based on non-olfactory information, enhancing the detection and discrimination of odors in complex environments.


Wednesday, February 3rd 2016
10:10 am:
Subject: To be announced

Wednesday, February 10th 2016
10:10 am:
Biophysics Seminar in 120 PAN
Speaker: Doug Smith, UC San Diego
Subject: Studies of motor-driven viral DNA packaging with optical tweezers: Biophysics of motor function and tight DNA confinement

In many viruses DNA is packed to near-crystalline density into ~50-100 nm prohead shells. The DNA is translocated into empty proheads by an ATP-powered molecular motor via a portal nanochannel, overcoming large forces resisting DNA confinement arising from DNA bending rigidity, electrostatic self-repulsion, and entropy loss. These biomotors are among the most powerful known, generating at least 20´ higher force than the skeletal muscle myosin motor. In addition to being of biological interest, viral packaging is an experimentally accessible model for investigating effects of spatial confinement on polymer dynamics, a topic of fundamental interest in polymer physics. We use optical tweezers to measure the packaging of single DNA molecules into single viral proheads. Our recent studies of phage phi29 have shown that: (1) The confined DNA undergoes nonequilibrium (glassy) dynamics with a very long relaxation time, causing slowing and pausing of the motor and heterogeneity in the packaging rate; (2) Contrary to theoretical predictions, net attractive DNA-DNA interactions mediated by +3 or +4 ions cause frequent stalling of packaging, which we attribute to a nonequilibrium jamming transition akin to that occurring in colloidal and granular soft matter systems; (3) Motor velocity is regulated not only by load force but also by a novel allosteric mechanism wherein ATP binding and motor pausing is regulated in response to changes in packaged DNA density and conformation. In addition, we investigate the motor mechanism by studying the effect of amino acid changes in the motor proteins. Our recent findings provide evidence for an electrostatic mechanism of force generation in the phage T4 motor and a role of ATP phosphate binding loop residues in mechanochemical coupling in the phage lambda motor, supporting recent structure-based models.


Wednesday, February 17th 2016
10:10 am:
Biophysics Seminar in 120 PAN
Speaker: Paul Tillberg, MIT
Subject: Expansion Microscopy-Improved Resolution Through Uniform Specimen Expansion
Note change from Journal Club to Seminar from previous announcement.

I will present Expansion Microscopy (ExM), a method in which the optical diffraction limit is circumvented by physically expanding a biological specimen prior to imaging. Expansion brings sub-diffraction limited structures into the size range viewable by a conventional diffraction-limited microscope. In ExM, proteins and visible probes are chemically anchored to an in situ-synthesized swellable polyelectrolyte gel. Proteolytic digestion is used to disrupt native tissue structures and enable uniform, 4.5-fold expansion of the material with anchored probes.

Known sub-diffraction limited structures are shown to have the expected shape and size, demonstrating that the expansion is isotropic down to the theoretically resolvable size scale of 70nm (pre-expansion). Optical scattering is dramatically reduced, allowing this resolution to be achieved throughout the depth of the specimen, limited only by objective lens working distance and the diffusion of the gel precursor. ExM is compatible with any optical microscope, and is simple to adopt into existing experimental workflows. ExM promises to be a powerful method for imaging neural circuits at sub-synaptic resolution, in addition to other types of biological specimens.


Wednesday, February 24th 2016
10:10 am:
Subject: To be announced.

Wednesday, March 2nd 2016
10:10 am:
Biophysics Seminar in 120 PAN
There will be no journal club due to the biophysical society meeting.

Wednesday, March 9th 2016
10:10 am:
Subject: Summary of the Biophysics Society Meeting

Wednesday, March 16th 2016
10:10 am:
Biophysics Seminar in 120 PAN
There will be no seminar this week, spring break.

Wednesday, March 23rd 2016
10:10 am:
Subject: To be announced.

Wednesday, March 30th 2016
10:10 am:
Biophysics Seminar in 120 PAN
Speaker: Allen Liu, University of Michigan
Subject: Mechanobiology of Membrane: from Mechanosensitive Channels to Artificial Cells

Biological membranes are involved in a large number of cellular processes including cell migration, membrane trafficking, and cell signaling. Significant amount of work have elucidated the molecular machineries that regulate dynamic membrane-based processes. In parallel, there are growing interests in recent years in trying to understand how mechanical state of the cells are utilized as a regulatory input to control cellular processes. My lab is interested in studying the mechanochemical responses of biological systems. In this talk, I will present two projects related to this theme. On the cellular level, we have reconstituted the function of a bacterial mechanosensitive channel MscL in mammalian cells. Using this system, we investigated the role of actin cytoskeleton in mediating local membrane tension that activates MscL. On the synthetic level, we are building artificial systems that can sense mechanical input and transduce a biochemical response. To this end, we are attempting to build artificial platelets that mimic the functionalities of natural platelets. I will discuss several modular platforms that we have developed that together will integrate into functional artificial cells. Together, our work will provide basic understanding of cellular mechanotransduction and potential applications of force-activated synthetic biology.


Wednesday, April 6th 2016
10:10 am:
Biophysics Seminar in 120 PAN
There will be no seminar this week.

Wednesday, April 13th 2016
10:10 am:
Subject: To be announced.

Wednesday, April 20th 2016
10:10 am:
Biophysics Seminar in 120 PAN
Speaker: Sarah Veatch, University of Michigan
Subject: Phases and fluctuations in biological membranes

The thermodynamic properties of plasma membrane lipids play a vital role in many functions that initiate at the mammalian cell surface. Some functions are thought to occur, at least in part, because plasma membrane lipids have a tendency to separate into two distinct liquid phases. We propose that these lipid mediated functions occur because plasma membrane composition is tuned close to a miscibility critical point at physiological temperature. This hypothesis is supported by our observations of micron-sized and dynamic critical composition fluctuations in isolated plasma membranes near room temperature. In this talk, I will discuss our ongoing efforts to probe for the existence and consequences of criticality in the plasma membranes of intact cells. These recent efforts include using quantitative super-resolution fluorescence localization microscopy to monitor the organization of plasma membrane proteins in B cell lymphocytes, both in resting cells and in cells stimulated with multivalent antigen against the B cell receptor. We also have identified a range of perturbations which alter both the magnitude of fluctuations in isolated vesicles. Some of these perturbations are also well characterized general anesthetics, and I will present evidence suggesting that some aspects of anesthetic function may be attributed to lipid heterogeneity.


Wednesday, April 27th 2016
10:10 am:
Subject: To be announced.

Wednesday, May 4th 2016
10:10 am:
Biophysics Seminar in 120 PAN
Speaker: Michael Guy Poirier, Ohio State University
To be announced.

Thursday, September 8th 2016
11:00 am:
Biophysics Seminar in 110 PAN
To be announced.

Thursday, September 15th 2016
11:00 am:
Biophysics Seminar in 110 PAN
There will be no seminar this week.

Thursday, September 22nd 2016
11:00 am:
Biophysics Seminar in 120 PAN
Speaker: Prof. David Piston, Washington University School of Medicine
Subject: Imaging the Molecular Mechanisms of Pancreatic Hormone Secretion
Note change of room from previous announcement.

The release of insulin from pancreatic β-cells plays a central role in maintaining normal blood glucose levels. Regulated trans-membrane gradients of calcium and potassium ion channels signal to increase or decrease insulin release. This is exemplified with the stimulation of dopamine, a neurotransmitter, which reduces intracellular calcium oscillations by activation of the dopamine receptor D3 (DRD3) and therefore inhibits secretion of insulin (Ustione & Piston, Mol. Endocrinol. 26, 1928 (2012)). We seek to better understand the physiological and cellular functions of dopamine signaling as it could potentially lead to a novel treatment of diabetes. DRD3 is a G protein-coupled receptor that we propose might interact with cellular ion channels through the Gβγ complex. Towards understanding which channels and pathways are involved, we have turned to quantitative imaging assays, the first of which is based on Förster resonance energy transfer (FRET), a technique widely used to study biomolecular dynamics and protein interactions in live cells. Limitations due to brightness differences, donor:acceptor stoichiometry, and cross-talk between the donor and acceptor can lead to misleading or even meaningless results. To help alleviate these problems with cellular FRET measurements, we have developed a new approach for absolute and high precision measurements of FRET efficiency is based upon the use of an optical switching acceptor. By employing a defined train of optical perturbations to control the on and off states of the acceptor, it is possible to modulate the fluorescence intensity of the donor, and this can be analyzed using a lock-in detection approach. Secondly, we have leveraged two-color Fluorescence Fluctuation Spectroscopy (FFS), which can be used to directly measure diffusion and binding rates of proteins within the cell. Using FFS to measure protein binding and diffusion allows quantification at the molecular level of protein interactions. In addition, protein molecular concentration can also be determined. Quantifying the molecular interactions within the proposed dopaminergic feedback pathway illuminates the signaling pathway, and thus provides essential information for developing a therapeutic treatment of non-insulin dependent diabetes.


Thursday, September 29th 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Prof. Marc Riedel University of Minnesota, Department of Electrical and Computer Engineering
Subject: T Computing with Crappy Clocks (C^3): A New Paradigm for Molecular Computing
Please note change of time from previous announcement. The seminar will be held at 11:15 for the remainder of the semester.

Clock distribution networks are a significant source of power consumption and a major design bottleneck for digital circuits, particularly with increasing variability. Completely asynchronous design methodologies have been studied for decades, but these have never gained widespread acceptance. We have proposed an alternative: splitting digital circuitry into small blocks and synchronizing these locally with independent, cheap clocks (generated with simple inverter rings). This is feasible if one adopts a stochastic representation for signal values. Logical computation is performed on randomized bit streams, with signal values encoded in the statistics of the streams. This talk will discuss extensions and applications of these ideas to molecular computing. DNA-based computation via strand displacement is the target experimental chassis.

Bio:

Marc Riedel is Associate Professor of Electrical and Computer Engineering at the University of Minnesota. From 2006 to 2011 he was Assistant Professor. He is also a member of the Graduate Faculty in Biomedical Informatics and Computational Biology. From 2004 to 2005, he was a lecturer in Computation and Neural Systems at Caltech. He has held positions at Marconi Canada, CAE Electronics, Toshiba, and Fujitsu Research Labs. He received his Ph.D. and his M.Sc. in Electrical Engineering at Caltech and his B.Eng. in Electrical Engineering with a Minor in Mathematics at McGill University. His Ph.D. dissertation titled "Cyclic Combinational Circuits" received the Charles H. Wilts Prize for the best doctoral research in Electrical Engineering at Caltech. His paper "The Synthesis of Cyclic Combinational Circuits" received the Best Paper Award at the Design Automation Conference. He is a recipient of the NSF CAREER Award.


Thursday, October 6th 2016
11:15 am:
Speaker: Prof. Kris Dahl, Carnegie Mellon University, Dept. of Chemical Engineering and BioMedical Engineering
Subject: To be announced.

Thursday, October 13th 2016
11:15 am:
Speaker: Yan Chen, School of Physics and Astronomy, University of Minnesota
Subject: Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus.”

Thursday, October 20th 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Prof. David Grunwald, University of Massachusetts Medical School
Subject: New imaging modalities and analysis approaches for life sciences

Historically, major advances in biology have rapidly followed major advances in microscopy, often driven by biologists' desires to visualize ever and ever smaller objects. Microscopy overcoming the diffraction limit and reaching single molecule sensitivity has revolutionized biochemical and biomedical research both in vitro and in vivo. Current day bioimaging techniques that allow for high xyz location precision do not allow for high time resolution and are extremely challenging in live cell applications; similarly, imaging modalities capable of high time resolution (milliseconds) are limited to monitoring a single xyz-plane. Thus, using current state of the art technology, it is impossible to track the complete 3D movement of intracellular macromolecules in real time.

Remarkably, high end imaging is not a standard tool in biomedical research like, for instance PCR or deep sequencing. A main cause for this might well be the degree of expert knowledge needed to analyze the images, which can present vexing issues in image analysis like limited signal, unspecific background, empirically set thresholds, image filtering and false-positive-detection limiting overall detection efficiency.
I present advances in real time simultaneous imaging for multiple parameters in the space and color domain and a new concept for quantitative analysis of original image data rather than of image derived meta-data.


Thursday, October 27th 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Lauren Jelenchick, University of Minnesota Medical School,
Subject: Centromere Mechanical Maturation: A New Theory for Regulation of Mechanical Signaling during Mitotic Progression
Note: change of speaker and program from last announcement.

Thursday, November 3rd 2016
11:15 am:
Speaker: Amanda Hayward, University of Minnesota, Dept. of Biochemistry, Molecular Biology and Biophysics
Subject: To be announced.

Thursday, November 10th 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Dr. Ruth Sommese University of Minnesota, Dept. of Genetics, Cell Biology & Development
Subject: Dissecting the regulation of collective myosin motility using DNA nanotechnology

While much is known about individual motor function, collective motility of molecular motors remains poorly understood. In the cell, myosin ensembles work together to drive numerous processes, from large-scale movement and force generation in muscle to dynamic cargo sorting to and from the cell membrane. Our lab is now developing tools to explore the regulation of myosin ensembles using DNA nanotechnology, which allows us to precisely control the biophysical properties of the motor-cargo interface. Complementing experimental approaches with computational modeling, highlights how the biophysical and structural properties of the acto-myosin interaction have been tuned to enhance collective motor behavior. Finally, we provide a novel method to pattern native protein complexes on DNA scaffolds using a GFP nanobody linkage. Overall, these approaches address an essential missing link in our understanding of collective motor function while also providing novel insight into the functional regulation of unconventional myosins.


Thursday, November 17th 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Razvan Chereji, National Institute of Child Health and Human Development
Subject: The Universality of Nucleosome Organization: From Yeast to Human

It is estimated that a human body contains about 100 trillion meters of DNA, enough to circle the Earth's Equator 2.5 million times. DNA is remarkably tightly packed inside the cell nucleus; nevertheless, transcription factors must quickly find and access the regulatory regions along the genome, should the need arise. Nucleosomes -- 147 basepairs of DNA wrapped around a histone octamer in about 2 turns -- are the basic units of DNA packaging. The precise positions of nucleosomes along the genome play an essential role in gene regulation, dictating which genes can be regulated by transcription factors. I study the nucleosome positions in various organisms (yeast, fly, mouse and human) and I build biophysical models that explain their organization. I will show that nucleosomes have a universal organization at the gene promoters, which is shared by multiple organisms, and that statistical mechanics can predict this common organization. I will show that DNA sequence alone has a limited effect in organizing the chromatin, and I will discuss the other mechanisms that have a major role in nucleosome positioning.


Thursday, December 1st 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Kevin Dorfman University of Minnesota, Dept. of Chemical Engineering and Material Science
Subject: The Physics of Genome Mapping in Nanochannels

Genome mapping by nanochannel confinement is an emerging method for obtaining large-scale genomic information at the single molecule level. In this method, large pieces of contiguous genomic DNA, hundreds of kilobase pairs in length, are labeled with a sequence-specific fluorescent probe while the backbone is labeled with a second color. Upon injection into a nanochannel, the labeled molecule stretches due to confinement and the locations of the probes (the “barcode”) are read by fluorescence microscopy.

Engineering DNA barcoding requires understanding two key properties: (i) the fluctuations of the DNA extension, which sets the lower bound for the error in reading the distance between barcodes; and (ii) the friction of the confined DNA, which set the minimum time scale for making uncorrelated measurements. While these quantities are well understood in the case of strong and weak confinement, nanochannel mapping takes place in moderate confinement, where the channel width is commensurate with the length scale for bending the DNA. This is a challenging regime for polymer physics, since there is no separation of length scales, and fluid mechanics, since there is no solution for the Green’s function of the Stokes equation in channel confinement. I will present our experimental and theoretical progress towards understanding the thermodynamics and hydrodynamics of this technologically relevant regime of confined polymers.


Thursday, December 8th 2016
11:15 am:
Biophysics Seminar in 120 PAN
Speaker: Prof. Wendy Gordon, University of Minnesota, Dept. of Biochemistry, Molecular Biology, and Biophysics
Subject: To be announced.

Thursday, December 15th 2016
11:15 am:
Speaker:  Prof. GW Gant Luxton, University of Minnesota, Dept. of Biochemistry, Molecular Biology and Biophysics
Subject: To be announced.

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