April 2023: Jacqueline Williams

Jacqueline Williams, a PhD student in the Bioinformatics program and member of the Hollenbach lab, presented her research on characterizing killer cell immunoglobulin-like receptor (KIR) genes in the context of multiple sclerosis.

Multiple sclerosis is a chronic inflammatory disorder that affects the central nervous system, and is likely caused by a combination of genetic, environmental, and molecular factors. The adaptive immune system has been implicated in disease pathogenesis, but more recently natural killer cells and their role in cytotoxicity and cytokine production have been associated with disease. NK cells function through cell-cell interactions mediated by cell surface receptors, most prominent of which are killer cell immunoglobulin-like receptor (KIR) genes that interact with HLA Class I ligands. The KIR complex, spanning 70-250 kbp, is the result of numerous gene duplications throughout human evolution, making it an incredibly diverse genomic region. This diversity includes high gene copy number variation, polymorphic alleles, and sequence similarity between genes. Due to that, characterization of KIR genes in the context of NK cells has been difficult to assess in a high throughput manner. The objective of this proposal is the characterize KIR genes in the context of multiple sclerosis patients by (1) performing an association analysis between KIR multiple sclerosis using a novel bioinformatics pipeline, (2) developing a long read sequencing method to inform haplotypic gene organization, and (3) evaluate binding affinity between KIR, their respective HLA Class I ligand, and foreign peptides

March 2023: Reuben Hogan

Reuben Hogan, a MD-PhD student in the Biophysics program and member of the Krogan lab, presented his research on capitalizing on advances in glycoproteomics to probe Alzheimer's Disease.

October 2022: Chase Webb

Chase Webb, a graduate student in the Pharmaceutical Sciences and Pharmacogenomics program and member of the Shoichet and Manglik lab, presented his research on traversing chemical space to understand opioid function.

Opioids are front-line analgesics and have been used for over 6000 years. Still, they have dose limiting liabilities including lethal respiratory depression, addiction, tolerance, and gastrointestinal disturbances. This project seeks to leverage exploding virtual chemical libraries and a growing structural understanding of the ┬ÁOR - the main target of clinical and illicit opioids -to design novel opioids devoid of the current limitations.

September 2022: Nadia Ayad

Nadia Ayad, a graduate student in the Bioengineering program and member of the Weaver lab presented her research on how the mesoderm is specified through beta-catenin dependent forces unfurling and delimited by programmed cell death in hESC gastrulation model.

How do mechanical forces present during gastrulation set the pattern of germ-layer boundaries? We set out to answer this question using confined human embryonic stem cells in soft gels and differentiating them with BMP4 in a 2-D gastrulation in vitro model. Previously, we had found that increased cell-cell tension at the periphery of these colonies is necessary for initiating a beta-catenin (╬▓-cat) dependent mesoderm program. When we looked at the inner ring of cells that would not express the early mesoderm marker Brachyury (T), we found an accumulation of apoptotic cells that was mutually exclusive and proximal to the outer ring of T expression. Upon caspase inhibition, we observed elevated cell tension and, after differentiation, a subsequent disorganization and increase in the boundary of T. Since tension is required to initiate mesoderm signaling, a tension release upon programmed cell death (PCD) may lead to less T. Indeed, inhibiting cell tension both reduced PCD and subsequent T expression. Interestingly, while apoptotic genes were not differentially expressed between T- and T+ cells, phagocytic receptors were more highly expressed in T- cells, pointing to an additional role of apoptotic cell recognition in mesoderm signaling. To test this hypothesis, we blocked phosphatidylserine binding with a high dose of AnnexinV and showed that it severely disorganized and increased T expression. This indicated that apoptotic cell recognition, and not just its mechanical role, may play an inhibitory role in the expression of the mesoderm marker T and regulate the boundary of its signal, which we will further explore.

May 2021: Jasmine King

Jasmine King, a graduate student in the Bioengineering program, member of the McDevitt Lab and a Career and Development Officer for BE-STEM, presented the talk titled: Modeling the Impact of the Autonomic Nervous System on the Development of Human iPSC-Sinoatrial Nodal Cells

Abstract: My research in the McDevitt Lab focuses on developing an iPSC-derived model of the Sinoatrial Node (SAN) to study the influence of innervation on SAN development and responsiveness to neuronal stimulation. The SAN is innervated by the autonomic nervous system; furthermore, the timing and chronology of cardiac innervation are evolutionarily conserved among most mammals, which suggests an important role for innervation in cardiac development. It has been difficult to study SAN innervation in vivo because chemical denervation approaches have systemic repercussions, and surgical denervation is technically challenging. To address the challenges of SAN models, I am leveraging the capabilities of iPSCs in order to study the impact of the autonomic nervous system on the development of iPSC-sinoatrial nodal cells.

April 2021: Christina Stephens

Christina Stephens, a graduate student in the Biophysics program and an Outreach Officer for BE-STEM in the Grabe lab, presented the talk titled: Investigating the Atomistic Mechanisms of TMEM16 Scramblases

Abstract: Membrane lipid composition plays a central role in establishing the physical characteristics of cellular membranes and changes in this composition initiate important cell signaling events such as platelet aggregation and apoptosis. One of these changes is the collapse of lipid asymmetry across the membrane carried out by members of the Ca2+-activated transmembrane protein 16 (TMEM16) family of lipid scramblases. Molecular dynamics (MD) simulation offers a way to study the atomistic interactions of the lipids and protein that could aid in determining the scrambling mechanism. Although several members of the field have been able to visualize full lipid translocation events using MD simulations, the events are rare enough that only a handful of observations have been made. To overcome this shortcoming, we employed an enhanced sampling method called Weighted Ensemble (WE) to enrich these rare events thereby generating an ensemble of pathways from which we can extract both the kinetics and energetics of the translocations.

March 2021: Chase Webb

Chase Webb, a graduate student in the Pharmaceutical Sciences and Pharmacogenomics Program in the Manglik and Shoichet lab and the co-president of BE-STEM, presented the talk titled: Traversing Chemical Space to Understand Opioid Function

Abstract: Opioids are front-line analgesics and have been used for over 6000 years. Still, they have dose limiting liabilities including lethal respiratory depression, addiction, tolerance, and gastrointestinal disturbances. This project seeks to leverage exploding virtual chemical libraries and a growing structural understanding of the ┬ÁOR - the main target of clinical and illicit opioids -to design novel opioids devoid of the current limitations.

February 2021: Muryam Gourdet

Muryam Gourdet, a graduate student in the TETRAD program and in the Narlikar lab, and an Outreach Officer for BE-STEM, presented the talk titled:  Incomplete chromatin particles are a preferred substrate for a conserved chromatin structure

Abstract: DNA dependent processes, such as transcription, are highly regulated by various factors including chromatin structure. The dynamic nature of this structure is regulated by ATP-dependent molecular motors (chromatin remodelers). I study the mechanisms that regulate the highly conserved chromatin remodeler, INO80. I unveiled that this remodeler preferentially acts on an incomplete chromatin particle providing biochemical evidence to support the model that INO80 restores chromatin disrupted by factors including RNA polymerase.

December 2020: Joel Babdor

Dr. Joel Babdor, a postdoc in the Spitzer Lab presented their work on high-throughput, high-dimensional technologies and computational methods to study the interactions between the human immune system and the microbiome at the systems level. He is also one of the co-founders of @BlackInImmuno on twitter.