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 – 9/30/2024

Total Funding: $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 expand UVA’s leadership in Cryo Electron Microscopy research, the most advanced method to determine atomic resolution 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. UVA has positioned itself at the forefront of this technology by establishing a regional NIH supported cryo-EM Center in 2017. Dr. Ed Egelman is a pioneer in this area and a member of the National Academy of Sciences; Dr. Jochen Zimmer who uses cryo-EM as his main research tool became a Howard Hughes Investigator in June 2022; and Ahmad Jomaa who was recruited with support from this SIF was selected by the Kinship Foundation in May 2023 to become the first ever Searle Scholar at UVA. 

The purpose of this award is to fortify UVA’s strength in this area by hiring a couple of new tenured or tenure-track faculty who are recognized experts in the field. After a pandemic related delay, we hired Dr. Ahmad Jomaa in February 2022. He has done spectacularly well in only 15 months he has been here. He was named the first Searle Scholar at UVA and he already published papers in Science, Nature Struct Mol Biol, and Nature Communications since arriving at UVA. Dr. Jomaa who joined us from the ETH Zurich uses cryo EM at the single molecule level to study large complexes such as ribosomes focusing on the mechanism of co-translational protein synthesis in mitochondria and its implications in cancer. 

In the current academic year, we posted a position to hire another tenure-track faculty member in Cryo Electron Tomography. Rather than looking at single molecules, cryo-ET seeks to determine cellular structures at the highest possible resolution in rapidly frozen cells and tissues. This is an emerging field and there are only few highly qualified individuals on the market. We zoom interviewed 10 candidates and selected 5 from Harvard, Berkeley, Scripps, Stanford, CalTech, and UCSD for on grounds interviews. We made a very generous offer to the top candidate and after a dragged-out competition with the University of Chicago and University of Colorado, Boulder, the candidate ultimately decided to go to Chicago. By the time this decision was made our next ranked candidates had found positions elsewhere. The current no cost extension will be used to search in this same field again. We expect to be successful this time because a critical piece of equipment, a cryo FIB SEM, for cellular sample preparation has been ordered and will be installed at UVA in Fall 2023.