Seminars, Defenses, & Special Events
Fall 2023 Biological Sciences Seminar Schedule
September 11 - Ellinor Haglund, Ph.D.
University of Hawaiʻi at Mānoa
Assistant Professor, Department of Chemistry
"The Folding and Function of Proteins with Complex Topologies"
Abstract: Folding of proteins into their active 3D-structure occurs spontaneously or is assisted with the help of chaperones within a biologically reasonable time, from micro- to milliseconds. It occurs within different compartments of the cell, controlled by the chemical environment. When folding goes wrong in cells, misfolded and/or aggregated proteins may arise, unable to perform their specific biological function. The correlation between structural motifs and their 3D-structure has been established to influence biology. However, less is known about the biological implications of protein topology, i.e., motifs that can act as a structural switch in response to environmental changes. Leptin is the founding member of the Pierced Lasso Topology (PLT), a newly discovered protein family sharing the unique features of a "knot-like" topology. A PLT is formed when the protein backbone pierces through a covalent loop formed by a single disulfide bond. PLTs are found in all kingdoms of life, with 14-different biological functions, found in different cell compartments. Despite the large number found in nature, where more than 600 proteins have been found with a PLT, a connection between topology and biological function has not yet been determined. We investigate three biological systems, the hormone leptin, chemokines, and the oxidoreductase superoxide dismutase (SOD1) and the association between the threaded topology and the biological function. Our results show that a PLT may control conformational dynamics switching biological activity on/off depending on the chemical environment. Thus, we propose that PLTs may act as a molecular switch to control biological activity in vivo.
September 18 - Jeffrey Amack, Ph.D.
Upstate Medical University
Associate Professor, Department of Cell and Developmental Biology
"Mechanical Forces Impact Morphogenesis of the Left-Right Organizer"
Abstract: The Amack Lab has a long-standing interest in understanding organ morphogenesis during embryonic development. Several projects are focused on investigating mechanisms that control form and function of a transient organ referred to as the 'left-right organizer' (LRO) that orients the left-right body axis of vertebrate embryos. In the zebrafish embryo, the precursor cells that give rise to the LRO (which is called Kupffer's vesicle) can be tracked and manipulated in living embryos. Interestingly, our work, and work from others, indicated LRO morphogenesis is a complex multi-layered process that appears to be regulated by several mechanisms that involve both biochemical signals and biophysical forces. The zebrafish LRO develops in a complex and dynamic environment, where it experiences biochemical cues, cell movements, and tissue-tissue interactions. By taking multiple approaches, which include mathematical modeling, quantitative live imaging, gene targeting, and embryological manipulation, we are using the zebrafish LRO to understand and tease apart complementary and/or redundant mechanisms that drive complex developmental programs in vivo.
September 25 - Alexey Khodjakov, Ph.D.
NYS Department of Health, Wadsworth Center
Cellular and Molecular Basis of Diseases - Mitosis
"Mitotic Spindle Assembly in 2023: From Random Search to Determination"
Abstract: The goal of cell division is to segregate genetic material, in the form of chromosomes, equally into the two daughter cells. To achieve this goal, each chromosome must physically connect with the two poles of the mitotic spindle, a macromolecular machine responsible for delivering the two molecules of DNA within the chromosome (i.e., 'chromatids') to the opposite poles. Research in my laboratory aims to reveal the mechanism(s) that allow these connections to form rapidly yet with minimal number of errors. Most recently we used a combination of live-cell recordings, correlative 3D light/electron microscopy, and computational modeling to analyze behavior of chromosomes in human cells under various experimental conditions. Based on these investigations, we formulate a novel model for mitotic spindle assembly. In contrast to the conventional view that various chromosomes within a cell connect to the spindle poles at random, our model envisions formation of these connections as a deterministic process in which connections to the poles appear synchronously on multiple chromosomes. This happens at a specific stage of spindle assembly and at a defined location determined by the spindle architecture. Experimental analyses of changes in the kinetochore behavior in cells with perturbed activity of molecular motors CenpE and dynein confirm the predictive power of the model.
October 2 - Annalisa Scimemi, Ph.D.
Associate Professor, Department of Biological Sciences
"Perseverance Versus Cognitive Flexibility: Neuronal Glutamate Transporters Give Us a Reason Not to Indulge in Either"
Abstract: Understanding the function of glutamate transporters has broad implications for explaining how neurons integrate information and relay it through complex neuronal circuits. Most of what is currently known about glutamate transporters, specifically their ability to maintain glutamate homeostasis and limit glutamate diffusion away from the synaptic cleft, is based on studies of glial glutamate transporters. By contrast, little is known about the functional implications of neuronal glutamate transporters. The neuronal glutamate transporter EAAC1 is widely expressed throughout the brain, particularly in the striatum, the primary input nucleus of the basal ganglia, a region implicated with the execution of habitual actions. Here, we show that EAAC1 limits synaptic excitation onto a population of striatal medium spiny neurons identified for their expression of D1 dopamine receptors (D1-MSNs). In these cells, EAAC1 also contributes to strengthening lateral inhibition from other D1-MSNs. Together, these findings shed light on some important molecular and cellular mechanisms implicated with behavior flexibility in mice.
October 16 - Scott Forth, Ph.D.
Rensselaer Polytechnic Institute
Assistant Professor, Department of Biological Sciences
"Deciphering the Mechanical Code in Complex Microtubule Networks"
Abstract: Cells must complete intricate mechanical tasks during a wide variety of biological processes ranging from the segregation of chromosomes during mitosis to forming and maintaining the axon and dendrites in neurons. To accomplish these diverse tasks, cells have evolved complex networks of force-generating and load-bearing elements in the form of the dynamic cytoskeleton. Consisting of elements such as microtubules, actin filaments, and a host of motor and non-motor proteins, these networks can perform mechanical work and transmit forces that push and pull cellular components. These networks span micron-scale distances, yet are built from nanometer-sized proteins that are 1000s of times smaller than the network itself. How these individual "building blocks" work collectively as ensembles to perform distinct mechanical tasks and allow the cell to maintain its structural integrity under load is unclear, as directly characterizing forces in this context has proved challenging. The Forth lab aims to bridge this critical knowledge gap by building these networks out of purified components and directly measuring their response to applied forces using biophysical tools such as optical tweezers and single molecule fluorescence microscopy. In this talk, I will describe how our lab at RPI has worked to understand the mechanical functions of essential microtubule crosslinking proteins across a range of biological processes.
November 6 - Benoit Boivin, Ph.D.
SUNY Polytechnic Institute
Associate Professor, Department of Nanobioscience
Seminar Title: Coming Soon
Abstract: Coming Soon
November 13 - Ken Halvorsen, Ph.D.
Senior Research Scientist, The RNA Institute
"Pulling on Individual Biomolecules with Centrifugal Force"
Abstract: Probing individual biomolecules such as proteins and nucleic acids with force continues to shape our understanding of how biological molecules stretch, deform, move, reconfigure, and interact with each other. However, such experiments can be technically challenging, tedious, and costly. Here, I will discuss the conception, design, and continued development of the centrifuge force microscope (CFM), an instrument designed to increase the throughput and the accessibility of single-molecule experiments. I will then dive into applications and uses of the CFM, focusing on a recent study in my lab measuring individual stacking energies between bases in DNA and RNA.
November 20 - Emily Le Sage, Ph.D.
Associate Professor, Department of Biology
Seminar Title: Coming Soon
Abstract: Coming Soon
December 4 - Francesca Massi, Ph.D.
UMass Chan Medical School
Associate Professor, Department of Biochemistry and Molecular Biotechnology
"Probing the Protein Dynamics of Profilin-1 and TDP-43: Function and Dysfunction in Two ALS-linked Proteins"
Abstract: Profilin-1 (PFN1) and TDP-43 are two proteins that have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We have used a combination of NMR spectroscopy and molecular dynamics (MD) simulation to characterize their structure and dynamics in solution. We observed that two ALS-linked mutations of PFN1, G1118V, and M114T, impact the internal dynamics of the protein, and therefore have the potential to impact the interaction of PFN1 with its binding partners actin and formin. For TDP-43, we have identified a core nucleus of structure for a folding intermediate in its second RNA recognition motif (RRM2). Our studies suggest a role for this RRM2 intermediate in normal TDP-43 function as well as in dysfunction by serving as a template for misfolding, aberrant interactions and aggregation.