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UCSD professor to receive $9M to study cellular protein

Posted at 1:44 PM, Sep 23, 2021
and last updated 2021-09-23 16:44:40-04

SAN DIEGO (CNS) — UC San Diego Associate Professor Elizabeth Villa Thursday was selected as a 2021 Howard Hughes Medical Institute investigator and will receive around $9 million over a seven-year term, renewable pending a scientific review.

Villa, a professor in UCSD's division of biological sciences, is one of 33 scientists representing 21 institutions chosen out of pool of more than 800 candidates.

A biophysicist who develops novel visualization techniques to explore the inner mechanisms of cells, Villa's investigations include deciphering the structure and function of the protein known as leucine-rich repeat kinase 2 -- the main genetic driver of Parkinson's disease.

Villa's techniques help visualize cellular machinery, like the molecules that transport compounds within cells and through their membranes.

Such machinery consists of bulky molecular complexes made up of proteins, carbohydrates, lipids and nucleic acids. Early in Villa's career, she began building the microscopy and computational tools needed to understand all those parts in action.

"We want to find ways to look at these molecules and their mechanisms in context -- inside of cells," she said.

Villa and her colleagues helped develop a technique called cryo-FIB milling.

First, researchers use a focused ion beam to blast ultrathin layers off frozen cells. They then take images of the sample from various angles using a transmission electron microscope. Computational tools combine those two- dimensional images into a 3D picture -- or tomogram -- of cellular structures in their natural environment.

Villa and her team use this technique -- and related cryo-electron microscopy and visualization methods -- to examine everything from bacterial transport structures to human proteins linked to disease.

Her lab recently determined the structure of the human LRRK2 protein, which drives Parkinson's disease. Until then, the protein had eluded scientists' efforts to study its structure.

Now her team plans to investigate LRRK2's function and whether it plays a role in transporting cellular compounds.

Villa and her fellow 2021 investigators were selected for their "potential to radically change how we think about biology, human health and disease," a statement from the Howard Hughes Medical Institute said.

HHMI will invest at least $300 million in these new investigators, who will join the investigator community or around 250 scientists.

"HHMI is committed to giving outstanding biomedical scientists the time, resources and freedom they need to explore uncharted scientific territory," said Erin O'Shea, HHMI president.

By employing scientists as HHMI investigators, rather than awarding them research grants, she says, the Institute is guided by the principle of "people, not projects."

HHMI selected the new investigators because they're thoughtful, rigorous scientists who have the potential to make transformative discoveries over time, said David Clapham, HHMI's vice president and chief scientific officer.

"We encourage investigators to follow new directions, learn new methods, and think in new ways," he said. "This could lead to scientific breakthroughs that benefit humanity."

To date, 32 current or former HHMI scientists have won Nobel Prizes -- most recently, Jennifer Doudna in 2020 for the development of a method for genome editing. Investigators have made significant contributions across many research areas, including HIV vaccine development, microbiome and circadian rhythm research, immunotherapy, SARS-CoV-2 biology, and potential therapies and vaccines for COVID-19, among other fields.