Cryo-EM

Cryo-EM

SIF 168 Cryo-EM

Project Manager: Lukas Tamm

The purpose of this award is to fund the start-up recruitment package for a key hire in the area of structural biology.

Approved: Summer 2019

Project Dates: 10/01/2020 – 9/30/2023

Funding Awarded: $1,650,000

Executive Summary

Cryo Electron Microscopy (Cryo-EM) is the most burgeoning new technique in the arsenal of methods to elucidate atomic structures of biomolecules (proteins, DNA, RNA, carbohydrates), viruses, and ultrastructure of cells at unprecedented resolution. Although EM of plastic embedded or negatively stained biological materials that produce images at lower resolution is older, two breakthroughs in the last decade or so have elevated biological EM to new levels. First, methods were developed to ultra-rapidly freeze and preserve biological samples in vitreous, i.e. glassy rather than crystalline ice, and second, a new generation of direct electron detectors were invented that obviated the need to convert electrons into photons for detection on photographic film or conventional CCD cameras. These two inventions, which were honored by the Noble prize in Chemistry in 2017, coupled with new methods of data analysis led to the so-called “resolution revolution” in structural biology. Since then the number of cryo EM structures solved has grown exponentially, and almost every issue of the leading journals Nature and Science reports on a new impactful cryo-EM structure.

UVA has positioned itself early and well in this field, through its current faculty. To maintain the momentum and to continue to be a leading institution and regional center in this field, this award enables the hire of one or two outstanding new faculty members with expertise in cryo-EM.

Current Status: Active

Progress

The goal of this project is to keep UVA at the forefront of research in Crye Electron Microscopy, the most recent and most advanced method to determine atomic structures of biomolecules and viruses, as well as the ultrastructure of cells at unprecedented resolution. This technology was awarded the Nobel Prize in Chemistry in 2017 and one of the laureates, Dr. Richard Henderson, gave a virtual lecture at UVA on March 22, 2021  (https://www.youtube.com/watch?v=YHp6NlVXCRg). UVA has positioned itself at the forefront of this technology by establishing a regional NIH supported cryo-EM Center in 2017. Dr. Ed Egelman who is a pioneer in this area was elected to the National Academy of Sciences in 2019 and Dr. Jochen Zimmer who is using cryo-EM as his main tool to elucidate the structural basis of carbohydrate biosynthesis became a Howard Hughes Investigator in June 2022, one of the most prestigious awards for a biomedical scientist. Drs. Owen and Barbie Pornillos are also well-established senior investigators in this area and Dr. Stefanie Redemann is a very successful tenure-track assistant professor using electron tomography as her main tool and who will come up for promotion soon. Dr. Mark Yeager who first established our cryo EM facilities is retiring from UVA at the end of October to become Director of the Frost Institute at the University of Miami.

The central purpose of this award is to fortify and maintain strength in this area by hiring a couple of new tenured or tenure-track faculty who are recognized experts in the field. As a first step, we hired Dr. Ahmad Jomaa in February 2022. Dr. Jomaa came to us from the ETH Zurich, Switzerland (the Swiss equivalent of MIT or Cal Tech). He is an outstanding single molecule cryo electron microscopist focusing on the mechanism of co-translational protein synthesis at the endoplasmic reticulum and mitochondria and their implications on cancer. Dr. Jomaa is a young star in this field. He has published multiple papers in Science and Nature titles and already submitted a paper to Nature Microbiology as the senior author since he has taken the position at UVA. He was recently selected by the VPR's office to submit an application for the prestigious Searle Scholarship award; Searle allows only one applicant from each institution.

In January 2022 the Department of Molecular Physiology and Biological Physics received permission from Dean Kibbe to hire a new faculty member in Crye Electron Tomography. This search is highly targeted and there are only small numbers of appropriately qualified candidates on the market in this emerging area. We hope to have the position filled by May or June 2023.