Keynote Speakers
September 9, 2023
Abstract:
The promise of precision medicine is to tailor treatments based on each individual’s genes and environment. However, current technology for determining individual genetic risks is limited. One cause is the bias and incompleteness of our methods for determining and reporting genetic variants from sequencing data. A key source of the bias in these methods is the reference DNA sequences that comprise the current human reference genome. I will discuss the creation of a human reference pangenome, that aims to rectify this bias. Coupled with the pangenome reference is the need for new pangenomic methods.
I will discuss our work to improve variant discovery, which we believe to be amongst the highest impact near-term “killer” applications of the pangenome. Further, I will propose the idea of personalized pangenomes as the substrate upon which future studies of individual genomes will be made.
Dr. Benedict Paten is an associate professor in the department of Biomolecular Engineering at the University of California, Santa Cruz. He is also an associate director of the UC Santa Cruz Genomics Institute. He received his Ph.D. in computational biology from the University of Cambridge and the European Molecular Biology Laboratory. Dr. Paten’s work is broadly focused on the growing field of computational genomics. He is involved in a number of large-scale efforts, he is currently a PI of the Human Cell Atlas Data Coordination Platform, the NHGRI AnVIL, HuBMAP, GENCODE, and the Human Pangenome Reference Consortium. Through these efforts and many smaller collaborations he is helping to develop methods to further our ability to assay and understand genomes.
Visualizing macromolecules in cells with cryo-EM
Abstract:
Cells are the fundamental unit of life. All cellular functions are mediated by composition, structure, and interactions of macromolecules, most notably proteins, and their complexes. Therefore, visualizing molecular structure, interactions, and location within the cell is necessary to understand the mechanisms underlying key cellular processes. Cryogenic electron microscopy (cryo-EM) can generate atomic resolution views of thin cell sections in near native conditions, making it a potentially powerful approach to visualize cells at molecular detail. However, cryo-EM images of cells have extremely low signal-to-noise, making them difficult to interpret directly. I will describe how I am using existing structural databases to locate and characterize macromolecular structure in cryo-EM images of cells in an approach called 2D-template matching (2DTM). In 2DTM an atomic model from a previous experiment or structural prediction is used to simulate how the structure would appear in the image (a template). Comparing all possible iterations of the template with a cryo-EM image can identify significant detections that correspond to the target molecule of interest. Specifically, I will describe how we can use these approaches to visualize large ribosomal subunit assembly in the yeast nucleus and characterize drug binding to a target molecule directly in cells.
Bronwyn Lucas is an assistant professor of biochemistry, biophysics and structural biology in the Department of Molecular and Cell Biology and Center for Computational Biology. Lucas’ research uses cryogenic electron microscopy (cryo-EM) to visualize cells at atomic resolution. Over the past decade there has been a significant increase in atomic-resolution structural models of macromolecules, thanks in large part to cryo-EM and machine learning tools like Alphafold2. This has created a vast repository of experimentally determined and predicted protein structures, akin to a “structureome,” which could serve as a reference for the biological community, much like the genome. The Lucas Lab develops new approaches to leverage the growing compendium of atomic-resolution structures and atomistic models to investigate the molecular details of life using cryo-EM. Bronwyn Lucas earned a Doctor of Philosophy (PhD) in Biochemistry and Molecular Biology from University of Rochester and was a postdoc at HHMI Janelia Research Campus and the University of Massachusetts Medical School.