The 5th Annual Next Generation in Biomedicine Symposium brings together emerging, talented scientists at the intersection of biomedical disciplines, to share their research and discuss exciting new directions. Twenty young scientists will present their innovative research across a wide range of fields relevant to biomedicine, including biology, chemistry, biomedical engineering, and AI/machine learning.
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Postdoctoral Fellow, University of Minnesota
Directed evolution reveals the functional flexibility of the ribosome
We have employed in vitro directed evolution to investigate various aspects of ribosome operation. Our studies suggest that ribosome motion, catalysis and specificity are considerably flexible properties. These results can inform the origin, function and engineering of the protein synthesis machinery.
Helen Hay Whitney Postdoctoral Fellow, Stanford University
Whole-Lifespan Behavioral Tracking and Modulation to Reprogram Organismal Lifespan
Aging is the number one risk factor for neurodegeneration, heart disease, and cancer. While our daily behaviors are key to homeostasis and survival, little is known about how behavior shapes aging and longevity. To investigate this, I leveraged an extremely short-lived vertebrate model, the African killifish (3–6-month lifespan), to continuously track and modulate behavior from adolescence until death to generate an unprecedented view into an animal’s aging, lifespan, and death.
HHMI Hanna Gray Postdoctoral Fellow, University of Colorado School of Medicine
Using cryo-EM to visualize conformationally dynamic RNA structures in viral genomes and their interactions with host proteins
RNA viruses use multifunctional, structural elements in their untranslated regions to hijack cellular machinery, but detailed mechanisms can be difficult to understand due to the dynamic nature of RNA structure. Because of its ability to resolve multiple conformational states, cryo-EM promises dissection of RNA dynamic structural landscapes in a way not previously possible. Using cryo-EM, we solved the structure of a ~55-kilodalton tRNA-like structure at the 3' end of the brome mosaic virus genome and visualized conformational changes that allow this structure to be recognized and aminoacylated by cellular tyrosyl-tRNA synthetase.
Postdoctoral Fellow, Stanford University
Design, validation, and application of complex synthetic microbiome
We construct and optimize a defined consortia of 119 human gut bacterial strains (hCom2) that largely recapitulates the phylogenetic diversity, ecologic stability, metabolic and immune function of native human microbiota. We then engineer hCom2 to modulate circulating levels of secondary bile acids in the murine host. Overall, our study demonstrates that hCom2 is a valid, engineerable model microbiota that can be used for mechanistic interrogation of microbiome-associated phenotypes.
NSF Postdoctoral Fellow, The Scripps Research Institute
Using 3D Variability Analysis to resolve some of nature’s most mysterious machines
Hepatitis C virus (HCV) causes chronic infection of the liver that can lead to cirrhosis or liver cancer. HCV infection affects around 71 million people worldwide and causes approximately 400,000 deaths each year. In my talk, I will present the first structure of the full-length HCV E1E2 glycoprotein complex, which offers hope for the development of a future prophylactic vaccine.
Postdoctoral Scholar, Weizmann Institute of Science
Engineering robust cheater prevention in bacterial differentiation via biphasic fitness
Differentiation is a key mechanism that multicellular organisms use to generate distinct cell functions but is also intrinsically prone to cancer-like mutants that never differentiate. A proposed theory for preventing such mutants is “biphasic fitness,” or quantitative coupling to an essential trait. I will discuss the development of a synthetic Escherichia coli differentiation system and the level of evolutionary robustness provided by biphasic fitness control.
Research Fellow, Harvard University
A cell type specific error correction signal in mouse posterior parietal cortex
Molecular studies have catalogued over fifty cortical cell types, but how these cell types contribute to cognition remains an open question. Using a cell type-specific adeno-associated virus, we identify a subset of somatostatin inhibitory neurons in mouse posterior parietal cortex that synchronously activate during navigational course corrections. We propose that this error-correction signal may aid the execution or learning of accurate goal-directed navigation trajectories.
Postdoctoral Associate, University of Pittsburgh
Stress response signaling acts as a metabolic sensor for reproduction
Reproduction relies on nutrient availability to support the high energetic cost of gamete production and reproductive behaviors, though the mechanisms that relay nutrient status to regulate reproductive output are not well understood. In the fruit fly Drosophila melanogaster, the conserved stress response factor ATF4 is active in highly metabolic cells such as adipocytes. Here, I will demonstrate that ATF4 in adipose tissue supports reproduction non-autonomously by 1) ensuring lipid/protein trafficking to the ovary and 2) promoting ovulation.
ASBMB Postdoctoral Scholar, Duke University
Stress-induced transposon mobilization in the human fungal pathogen Cryptococcus
Life-threatening fungal infections are on the rise due in part to climate change and increased spore dispersal. Recently we discovered that heat stress increases the mutation rate in an environmental fungus responsible for cryptococcal meningitis and AIDS-related deaths. Here, we investigate the contribution of mobile genetic elements in stress-induced adaptation, drug resistance and disease persistence.
Research Scientist, Massachusetts Institute of Technology
A Cultural Renaissance: Microbial devices as sensors, medicine and beyond
Microbes grow in and on everything, tuning the chemical make-up of animals, plants, and our environment. Yet today, we culture, study, and use them in only idealized settings. By leveraging microbes’ natural ability to function in non-model settings, we can embed them in devices to sense and treat disease with molecular specificity.
Postdoctoral Fellow, New York University School of Medicine
Initiation of diverse T cell programs in response to gut microbes
It is commonly accepted that classical dendritic cells (cDC) initiate all CD4 T cell responses. In my talk, I will present our recent findings showing that different CD4 T cell responses to gut microbes require distinct antigen-presenting cell subsets. I will also challenge the current dogma and show that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells is required and sufficient for the induction of Treg cells.
Postdoctoral Researcher, Stanford University
Evaluating eligibility criteria of oncology trials using real-world data and AI
Clinical trials are the gate-keeper of medicine but can be very costly and lengthy to conduct. In this talk, I will first discuss Trial Pathfinder, a computational framework that simulates synthetic patient cohorts from medical records to optimize cancer trial designs (Liu et al Nature 2021). Trial Pathfinder enables clinical trials to be more inclusive, benefiting diverse patients and trial sponsors.
Postdoctoral Research Fellow, University of Washington
The sequence, structure, and evolution of human centromeres
For the past twenty years, the sequence of the human genome has remained unfinished due to the presence of large swaths of repeats clustered with centromeres, segmental duplications, acrocentric p-arms, and telomeres. However, recent advances in long-read sequencing technologies and associated algorithms have now made it possible to systematically assemble these regions from native DNA for the first time. Here, I present the complete sequence of each centromere in the human genome, and I provide an in-depth look at their structure and evolution over time.
Swanson Fellow, The Column Group
Stanford University | Improving prenatal care through liquid biopsies
Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and to bridge gaps in clinical care. Here we identified cfRNA transcriptomic changes that are associated with preeclampsia, a multi-organ syndrome that is the second largest cause of maternal death globally. This enabled the development of a liquid biopsy test that would identify mothers at risk of preeclampsia long before clinical symptoms manifest themselves. Tests based on these observations could help predict and manage who is at risk for preeclampsia—an important objective for obstetric care.
Postdoctoral Fellow, Harvard Medical School
Radical genetic code engineering for broad virus resistance and biocontainment of genetic information
Engineering the genetic code of Genetically Modified Organisms (GMOs) can provide isolation from natural ecosystems by preventing viral replication, horizontal gene transfer, and unintended escape. In this talk, I will illustrate how bottom-up genome synthesis followed by rational genetic code engineering simultaneously provides multivirus resistance, eliminates horizontal gene transfer into and out of GMOs, and tight biocontainment via dependence on an amino acid not found in nature.
Research Fellow, National Institute of Mental Health
Cell type composition of human mediodorsal thalamus and its implications for serious mental illness
The human mediodorsal thalamus, along with its reciprocal connectivity to the prefrontal cortex, has been implicated in the pathogenesis of serious mental illness, such as schizophrenia, autism, and bipolar disorder, but remains under-studied at the cellular and molecular level. We recently examined the cell type composition of the human mediodorsal thalamus using single-nucleus RNA-seq followed by multiplex in situ hybridization, revealing a major gene expression gradient that spans across its projection neurons and maps onto anatomical space, as well as several discrete neuronal subpopulations. Ongoing and future studies will investigate cell type-specific gene expression differences between psychiatric cases and controls, both in the mediodorsal thalamus and in its cortical target regions, and integrate these findings with genetic risk for schizophrenia and bipolar disorder.
American Cancer Society Postdoctoral Fellow, Stanford University
Targeting sugars for immunotherapy with antibody-lectin bispecifics
Tumors use sugars, or glycans, to evade the immune system. I will describe development of antibody-lectin bispecifics as a modular and programmable approach to target glycans for cancer immunotherapy.
Sandler Faculty Fellow, University of California San Francisco
Decoding communication across the blood-brain barrier
The blood-brain barrier impedes effective drug delivery to the brain and its dysfunction is a leading cause of neurological disease. In this talk, I will introduce our use of proteome tagging and sequencing approaches to reveal an unexpected degree of endogenous protein transport into the healthy brain and its role in brain aging and Alzheimer’s disease. These findings inform our ongoing efforts to decode the molecular logic of protein and immune cell communication between the brain and body.
Damon Runyon Postdoc Fellow, University of California San Francisc
Drugging K-Ras(G12D) with Targeted Covalent Inhibitors
KRAS is the most frequently mutated oncogene in human cancer. Especially a glycine-to-aspartate alteration at codon 12 of K-Ras is accountable for a majority of pancreatic ductal adenocarcinoma patients. We have developed the first small molecule to covalently modify Asp12 and inhibit the downstream signaling pathways, which leads to selective mutant cell killing.
Postdoctoral Scholar, Gladstone Institutes
Synthetic multistability in mammalian cells
Inspired by natural multistable circuits, we created MultiFate, a synthetic circuit that supports up to seven synthetic cellular states, each stable for at least 18 days. MultiFate permits controlled state-switching and modulation of state stability through external inputs, and can be expanded with additional transcription factors. These results provide a foundation for engineering multicellular behaviors in mammalian cells.