Vanderbilt investigators secure a grant from the Keck Foundation for groundbreaking genetic research

by Herschel Pollard

Vanderbilt University scientists Charles Sanders, PhD, and Roy Zent, ​​MD, PhD, received a $1.2 million award from the WM Keck Foundation for their groundbreaking project, Genetic Intolerance Patterns as a Treasure Map to Genes that Define Us as Human.

This groundbreaking project led by Professors Sanders and Zent underscores the caliber of transformative research we aim to foster at Vanderbilt, said John Kuriyan, PhD, dean of basic sciences at Vanderbilt University School of Medicine.

It is encouraging to see their pioneering work and collaborative spirit driving scientific progress at Vanderbilt University and Vanderbilt University Medical Center recognized by the WM Keck Foundation,” said Kuriyan.

Sanders, a structural biologist who studies the role of defective proteins in various diseases, is Professor of Biochemistry and Medicine, Aileen M. Lange and Annie Mary Lyle Chair in Cardiovascular Research, and vice dean of basic sciences at Vanderbilt University School of Medicine.

Zent is professor of medicine and cell and developmental biology, Thomas F. Frist Sr. Chair in Medicine and vice chair of medicine for research at Vanderbilt University Medical Center. His research has focused on integrins, cell adhesion receptors that are important in tissue formation and function.

Sanders started the project a few years ago when he asked his son, Adam Sanders, to sort and organize the genetic intolerance data of 20,000 human proteins.

The five-month effort, coupled with bioinformatics analysis by Jake Hermanson, a rolling student in Sanders’ lab, revealed 250 proteins containing large segments apparently intolerant of mutations in the human population. The discovery was published last year in the journal Protein sciencewith Adam Sanders and Hermanson recognized as co-first authors.

While some of these proteins are well known for being very important (for human biology), many others are poorly understood and understudied. It is these proteins that are most exciting to us previously buried treasure, said Charles Sanders.

Sanders and Zent will collaborate to characterize three of these little-known proteins to see if they are, in fact, super important. The project brings together their unique strengths and interdisciplinary collaboration, enabling them to probe selected proteins at multiple levels, from single molecules to whole animal physiology.

The $1.2 million grant will be instrumental in supporting this labor-intensive effort, which will involve extensive experimentation to discover the importance and functionality of these proteins.

This will be a heavy experimental project, Zent said. The funds will be used to pay for the personnel, supplies and basic services needed to perform these experiments at both the Sanders Laboratory (VU) and the Zent Laboratory (VUMC).

Despite anticipated challenges, including the potential difficulty of working with the selected proteins, the researchers are optimistic about their project’s potential. “This project should provide a rigorous test of whether genetic intolerance analysis really can be used to identify previously overlooked human proteins that are actually very important,” Sanders said.

The grant application process for the project involved close collaboration and painstaking work between multiple administrators at VU and VUMC.

Sanders recognized this, including the research, development and support effort within the Vanderbilt office of the Vice Chancellor for Research and Innovation, especially Janice Ascano, PhD, and Executive Director Joanne Spitz in collaborating with Keck Foundation, facilitating the application process and preparing their site visit presentation.

Research Development and Support offers a range of services to Vanderbilt researchers, including identifying potential sources of funding, assisting with grant proposal development, and coordinating multi-investigator proposals. For more information, emailrds@vanderbilt.edu.

The WMKeck Foundation was founded in 1954 in Los Angeles by William Myron Keck, founder of Superior Oil Co. One of the largest philanthropic organizations in the nation, the WMKeck Foundation supports outstanding scientific, engineering and medical research. The foundation also supports college education and maintains a program within Southern California to support arts and culture, education, health care, and community service projects.