DAVIS — The W.M. Keck Foundation has awarded $2 million in grants to the University of California, Davis, for research on cell mechanics and the genetics of common diseases.

Professors Gang-Yu Liu, Department of Chemistry, and Ian Kennedy, Department of Mechanical and Aerospace Engineering, received $1 million to develop a new instrument for measuring the mechanics of single cells and using it to study the toxicity of nanoparticles. Associate professor David Segal, Department of Pharmacology, was awarded $1 million to take a novel approach to identifying genetic changes associated with heart disease.

UC Davis is one of only three institutions to receive grants from the foundation’s medical research program this year, and one of only six institutions to receive grants from the foundation’s science and engineering research program.

Cell mechanics

Liu and Kennedy will use their grant to develop a microscope that can measure the stiffness and other mechanical properties of individual cells, as well as see activity inside them. The new instrument will combine a confocal microscope, which can focus on layers within a living cell, with an atomic force microscope, which can study surfaces in exquisite detail as well as press a tiny bead against a cell and measure its resistance.

“We are very excited to accept this grant and extremely grateful to the Keck Foundation for this and past support,” said Winston Ko, dean of the Division of Mathematical and Physical Sciences in the College of Letters and Science.

The foundation’s total philanthropic support to UC Davis exceeds $7.9 million, including previous major grants to faculty to support work on the Large Synoptic Survey Telescope in Chile and the Keck Center for Active Visualization in Earth Sciences, housed at UC Davis.

“I have every reason to believe that professor Liu’s research will lead to the same level of discovery and innovation,” Ko said.

Liu’s laboratory has already demonstrated the potential of the microscope concept in experiments with nerve cells, which become stiffer when they are affected by the prion proteins related to Alzheimer’s disease. The new instrument will be able to test a wider range of cell types and incorporate other features that make it easier to use with live cells, Liu said.

Liu and Kennedy now plan to use the microscope to test whether early signs of damage to endothelial cells — which line the blood vessels and airways, for example — show up as changes in the cells’ mechanical properties. The experiments will use novel nanoparticles made by Kennedy’s lab, which combine tiny particles of metal oxides — similar to particles that are widespread in the environment, and that are also becoming common in products such as sunscreens — with gold or other elements that allow the particles to be tracked within cells.

The new microscope will help to answer questions that are difficult to address with current technology. Zinc oxides, for example, are used in some sunscreens and also occur naturally in the environment. There is some evidence that they can cause damage to cells, but no clear scientific consensus about how serious the problem is, Kennedy said.

“The technology can also be further developed to study different areas,” Liu said. For example, cancer cells appear to be softer than normal cells, a property that the new microscope can measure — suggesting a potential new approach to cancer research, diagnosis and treatment monitoring.

"This award is a great recognition of professor Kennedy's extensive accomplishment in the study of the transport of ultrafine particles in tissues and organisms, and applying nanoscale particles to detection technologies in biology and biophotonics,” said Enrique Lavernia, dean of the College of Engineering. “This work offers great promise in diagnosis, monitoring and treatment of disease, and this opportunity will be greatly advanced with the Keck Foundation's support.”

Genetics and heart disease

Segal’s research focuses on understanding how single nucleotide polymorphisms, or SNPs (pronounced “snips”), contribute to disease. His goal is to understand how specific SNPs, which are tiny variations in the sequence of DNA, increase the risk of coronary artery disease in some people.

“It’s common to consider coronary artery disease a lifestyle disease,” said Segal, “yet we know that people with similar eating, exercise and smoking habits do not necessarily have similar risks. Our work is bringing more certainty to the molecular changes that actually put the cellular interactions into motion that lead to this disease.”

Segal’s lab creates custom enzymes that can make precise changes to SNPs in the DNA of living cells, then tests those changes within particular cell types. In the current study, he will assess the impact of various SNP sequences on endothelial cells, which form the interface between circulating blood and vascular tissues. Compared with healthy people, endothelial cells behave differently in patients with coronary artery disease, eventually allowing plaques to accumulate.

“Coronary artery disease is a highly complex condition, but if we can figure out what the DNA is telling our cells to do, we might be able to find ways to change its course,” said Segal.

“In selecting Dr. Segal for this grant, the Keck Foundation has recognized the enormous value of his work to human health,” said Claire Pomeroy, vice chancellor for human health sciences and dean of the School of Medicine at UC Davis. “His groundbreaking research will advance knowledge of coronary artery disease and lead to early interventions that can potentially save the lives of millions of Americans.”

Cardiovascular disease is the No. 1 cause of disease-related death in the United States. Current treatments focus on lifestyle changes, structural interventions such as stents, and medications that relieve symptoms; there currently are no treatments that affect the underlying causes of heart disease, however. Segal and his collaborators on the grant — Jan Nolta, director of the UC Davis Stem Cell Program; Anne Knowlton, professor of internal medicine; David Rocke, professor of public health sciences; and Scott Simon, professor of biomedical engineering — are changing that by identifying new molecular pathways that could serve as drug targets.

“With these latest grants, the Keck Foundation continues its longstanding partnership with UC Davis to foster innovation and discovery that advance health the world over. We are extremely grateful for their support,” said Pomeroy.

The Keck Foundation grants will count as part of the Campaign for UC Davis, a universitywide initiative to inspire 100,000 donors to contribute $1 billion in support of the university’s mission and vision. The campaign has already raised more than 70 percent of that total.

About the W.M. Keck Foundation

The W.M. Keck Foundation is one of the nation’s largest philanthropic organizations, and awards grants in the areas of science, engineering and medical research; undergraduate education; and Southern California arts, culture, education, health and community service projects.