Author: Xavier Larkin

Join the CQB & DMI for a special seminar with Dr. Yongshae Shin. Dr. Shin is an Associate Professor in the Department of Mechanical Engineering at Seoul National University, and an Adjunct Professor in the Interdisciplinary Program in Bioengineering and Department of Biological Sciences. The focus of Prof. Shin’s group research is to understand and engineer self-organization processes in living systems. Of particular interest are biomolecular condensation, especially its biophysical mechanisms and physiological functions. For this, he combines multiple approaches including single-molecule resolution quantitative imaging, reconstitution of biomolecular condensates both in test tube and in cellulo, and optogenetic manipulation of biological phase separation. He received his BS in Mechanical and Aerospace Engineering from Seoul National University, and MS/PhD degrees in Mechanical Engineering from Massachusetts Institute of Technology. He then went on to Princeton University as a Postdoctoral Research Associate in the Department of Chemical and Biological Engineering. He was selected as the World Economic Forum Young Scientist in 2019.

 

Abstract: Biomolecular condensates represent a condensed state of living matter, widely observed in various cellular processes. Condensates are composed of a set of distinct molecular components, organizing diverse biochemical reactions. How condensate function emerges from the collective interactions of its components remains elusive. In this talk, I will discuss our ongoing efforts to study the biophysical basis of condensate-driven cellular functions. I will first introduce density as a key parameter that can impact condensate function. Using refractive-index imaging, we uncovered that intracellular condensates exhibit a broad range of density, where RNA plays a key regulatory role in lowering condensate density. I will then switch to the second topic probing the effect of RNA condensation on translation activity. Using optogenetic cellular reconstitution, we found that condensation itself provides suppressive microenvironments for mRNA translation, and solidifying condensates further inhibits translation activities. Our works highlight an intimate link between the physical properties of condensates and associated biochemical functions.

Join the CQB for our last seminar series of the Fall 2024 semester on Friday, December 6, 2024 from 3-4:00 pm in Wilkinson 021.  We will be hearing from our guest speaker, Dr. Jim Pfaendtner.

Jim Pfaendtner is the Louis Martin-Vega Dean of Engineering at NC State University. Previously, Pfaendtner served as chair of the Department of Chemical Engineering at the University of Washington. His research focuses on using computer simulations to understand molecular behavior for applications in biotechnology and advanced materials. Pfaendtner earned his B.S. in chemical engineering from Georgia Tech and his Ph.D. from Northwestern University.

Abstract:

Peptoids, or n-substitued glycines, are complex and diverse oligomeric structures which have been explored for a number of biomimetic applications including drug delivery, surfactants, and catalysts. In contrast to their peptide counterparts, on peptoids the sidechain is bonded to the backbone nitrogen resulting in a flexible omega backbone dihedral that is able to isomerize into both stable cis- and trans- backbone conformations. This unique feature of peptoids allows for these structures to potentially span a significantly larger configurational space of chemical and structural functionality through the careful tuning of their side chains. This vast chemical and structural space has created significant challenges for rational design of new structures and functions as the underlying molecular scale driving forces that give rise to sequence/structure/function relationships have proven difficult to uncover.

This talk will highlight recent developments from our group in the use of statistical mechanical tools to accelerate molecular simulations of rare events like peptoid folding, aggregation and adsorption on inorganic surfaces. The first part of the talk focuses on studies of peptoid folding. Peptoids can freely explore a 12-dimensional helical configurational space with stabilization dictated largely by interactions between sidechains. I will discuss the thermodynamic basis of helix stabilization by chiral sidechains as well as fundamental aspects of the simulation science and the role of solvent in folding. Implications for rational design of higher order (tertiary structures) will be discussed. The remainder of the talk focuses on the use of peptoids in biomineralization. We discuss the rational design of peptoid mimics of the well-known R5/silaffin system, compare their nanoscale properties with peptides, and highlight experimental findings showing the efficacy of peptoids in biomineralization applications as well as similarities and differences between the peptoid and peptide systems. If available time remains, I will briefly discuss our group’s use of machine learning models to assist in high throughput screening towards inverse design of new sequences that precisely tune surface adsorption energies for biomolecules.

Join the Duke Center for Quantitative Biodesign on Friday, November 8, 2024 from 3-4:00 pm in Wilkinson 021 as we hear from our next guest speaker, Dr. Theresa M. Reineke.

Dr. Reineke is the Prager Endowed Chair in Macromolecular Science and a Distinguished McKnight University Professor in the Department of Chemistry at the University of Minnesota. She also holds graduate faculty appointments in the Departments of Chemical Engineering/Materials Science and Pharmaceutics. She received a B.S. Degree from the University of Wisconsin-Eau Claire, a M.S. Degree from Arizona State University, and a Ph.D. from the University of Michigan. She then received a National Institutes of Health Postdoctoral Research Fellowship for her work in gene therapy at the California Institute of Technology prior to beginning her independent faculty career.

Her research group is focused on enabling fundamental and applied technology advancements in the fields of macromolecules for nucleic acid delivery and gene editing, oral delivery of therapeutics, and sustainability. She has published over 200 peer-reviewed manuscripts and patents and manages a large group of researchers supported by several corporate, private and national funding agencies. Reineke is a Fellow of the American Chemical Society, Royal Society of Chemistry, along with the Kavli and Alfred P. Sloan Foundations. She has received numerous awards, including in the 2005 National Science Foundation CAREER and Beckman Foundation Young Investigator Awards, 2008 Camille and Henry Dreyfus Teacher-Scholar Award, 2009 National Institutes of Health Director’s New Innovator Award, 2012 Outstanding New Investigator Award from the American Society of Gene and Cell Therapy, 2017 Carl S. Marvel Creative Polymer Chemistry Award from the American Chemical Society Division of Polymer Chemistry, 2018 DuPont Nutrition and Health Sciences Excellence Medal, and 2022 Arthur C. Cope Scholar Award from the American Chemical Society. Reineke has also served for 11 years as an Associate Editor for the journals ACS MacroLetters and Chemical Science and in 2023 became Editor-in Chief of Bioconjugate Chemistry. Further, Reineke has cofounded three biotech companies in the field of nucleic acid delivery: Techulon, Inc., Nanite, Inc., and LiberateBio, Inc.

Join the Duke Center for Quantitative Biodesign on Friday, October 4, 2024 at 3:00 pm in Wilkinson 021. Our guest speaker, Dr. Alex Holehouse, is an Assistant Professor of Biochemistry and Molecular Biophysics at Washington University in St. Louis School of Medicine, where he will be discussing “Mapping from sequence to function in intrinsically disordered regions.”

The Holehouse Lab studies how biological function is encoded into intrinsically disordered proteins and how this goes wrong in disease. They use a combination of physics-based models, bioinformatics, deep learning, and quantitative cell biology.

Bio:  Alex received his Ph.D. Washington University in St. Louis, Computational Biophysics in 2017,  MsC. From Imperial College London, Computer Science in 2011, and his MBioch from University of Oxford, Molecular & Cellular Biochemistry in 2010.

Abstract:Intrinsically disordered protein regions (IDRs) are ubiquitous across all life kingdoms and play various essential cellular roles. Unlike folded domains, which are well-described by one or a small number of structurally similar states, IDRs exist in a collection of structurally distinct conformers known as an ensemble. While IDRs are ‘disordered’, they are not ‘unstructured’ – sequence-specific effects influence intra- and inter-molecular interactions that ultimately dictate biological function. Here, we will discuss recent advances that combine chemical physics, informatics, and deep learning to infer biologically important functions directly from sequence. These approaches offer opportunities for understanding IDR evolution, interpretation of disease-associated variants of unknown significance, and rationally designing functional IDRs with specific functional properties.

Join the CQB on Friday, September 27, 2024 from 3-4pm in Wilkinson 021,  as we kick off our fall 2024 semester with our first guest speaker, Dr. Hernan Garcia, Associate Professor in the Departments of Molecular & Cell Biology and Physics at University of California, Berkeley.

Bio: Hernan G. Garcia is an Associate Professor in the Departments of Molecular & Cell Biology and of Physics at UC Berkeley. As a Physical Biologist, his research aims to uncover the quantitative and predictive principles dictating biological phenomena, with particular emphasis on embryonic development. Hernan is a co-author of the textbook Physical Biology of the Celland has directed several courses at institutions such as the Kavli Institute for Theoretial Physics at UC Santa Barbara, and the Marine Biological Laboratory in Woods Hole, MA.

Abstract: Over the last few decades we have largely identified the repressors and activators that shape gene expression patterns in developing embryos and that, in turn, dictate cellular fates. Yet, despite amassing this great reservoir of knowledge, we are still incapable of predicting how the number, placement and affinity of binding sites for these transcription factors in regulatory DNA dictate gene expression patterns in space and time. Achieving such predictive understanding calls for going beyond molecular parts lists and for obtaining the in vivo biochemical information necessary for fueling theoretical models of transcriptional regulation in developing animals.

In this talk, I will show how we are using physics as a “microscope” to uncover the molecular mechanisms by which activators and repressors dictate transcription in space and time in developing animals. Specifically, using novel quantitative tools that we have developed for precision measurements, I will show that most developmental genes are transcribed in stochastic bursts, and that many transcription factors regulate gene expression by modulating the frequency, duration, and/or amplitude of these bursts. We will then engage in an iterative dialogue between theoretical models and quantitative experiments aimed at revealing the mechanisms underlying this control of transcriptional bursting. Our results challenge the textbook picture of activator and repressor action based on stable protein-protein interactions and call for a description of transcriptional control that acknowledges that the nucleus is not a bag of well-mixed transcription factors. Most importantly, our work sets a path forward for reaching a predictive understanding of cellular decision making and demonstrates how a quantitative dialogue between theory and experiment can shed light on biological mechanisms beyond the reach of even the best super resolution microscopes.

ICYMI: Congratulations to our very own, Dr. Veronica Ciocanel and her group, on their new paper “Minimal Mechanisms of Microtubule Length Regulation in Living Cells.”

The goal was to understand what controls microtubule length in dendrites of Drosophila neurons. We used experimental measurements and a stochastic mathematical model to study mechanisms such as limited tubulin availability and the dependence of shrinking events on microtubule length.

These are needed since experimental parameters predict unbounded growth! They also developed a reduced deterministic model that informed their choices of parameters for the more complex stochastic model. We hope to use this to further understand how microtubules collectively organize into polarized structures in neurons.

Read more here: https://link.springer.com/article/10.1007/s11538-024-01279-z

ICYMI: Congratulations to Lingchong You on his recent press release entitled, “Industrious Communities Can Create Cheaters, Even in Bacteria” that was supported by Office of Naval Research, the National Science Foundation and the National Institutes of Health.

Congratulations to Prof. Lingchong You on his recent paper that was featured in the science journal, Nature Communications , on  “Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria.”

Congratulations to our very own , Prof. Lingchong You, Director of The Center for Quantitative Biodesign and James L. Meriam Distinguished Professor of Biomedical Engineering on the You Lab’s recent press release regarding Copies of Antibiotic Resistance Genes Greatly Elevated in Humans and Livestock.