Grants fund high-risk research on fungal disease and antibiotic resistance

Two faculty members were awarded Schwartz Research Fund Visionary Grants to research the basic biology of fungi in order to potentially treat fungal disease; and to investigate cell-to-cell communication in bacteria, with potential implications for combatting antibiotic resistance.

The grants, made possible through support from Joan Poyner Schwartz '65 and Ronald H. Schwartz '65, will provide $300,000 each to Lori Huberman, assistant professor in the School of Integrative Plant Science, Plant Pathology and Plant-Microbe Biology Section and Heather Feaga, assistant professor in the Department of Microbiology, both in the College of Agriculture and Life Sciences.

The funding for faculty members in the life sciences aims to provide significant assistance for innovative, visionary research that opens an important new line of inquiry.

The Schwartzes, both chemistry majors in the College of Arts and Sciences prior to long careers as scientists at the National Institutes of Health, have dedicated themselves to promoting the work and careers of women in the life sciences. This year marks a decade of their grant donations to Cornell.

"As scientists who worked at the National Institutes of Health for 40 years, we saw young scientists facing many hurdles," Joan and Ronald Schwartz said in a joint statement. "This led us to endow the Schwartz Research Fund supporting faculty conducting life science research advancing Cornell's founding principle of '…any person… any study,' and specifically faculty who mentor our diverse students. We are pleased with the grants' outcomes over the past 10 years."

In addition to the Schwartz Visionary Grant, the couple supports the Schwartz Research Fund.

"We are extremely grateful to Drs. Joan and Ron Schwartz for their generous decade long support," said Avery August, Ph.D. '94, professor of immunology in the College of Veterinary Medicine and deputy provost. "Their giving has been impactful to our faculty who have been able to use the seed funds and visionary fund to advance leading edge discoveries."

Huberman will use her grant to investigate the mechanisms that fungi employ to invasively sense and grow toward a host, where they might then infect it. Specifically, she seeks to understand how fungi detect a host's nutrient signals.

Uncovering this basic biology of fungi may reveal future targets for disrupting these mechanisms and preventing disease. Each year, fungal pathogens kill about 3.8 million people, cause about 1 billion infections and are responsible for 30% of crop losses around the world.

"If a fungus couldn't find its host, then it wouldn't be able to infect it, and so maybe we could disrupt that sensing aspect," Huberman said.

Huberman and colleagues will use a fungus called Neurospora crassa as a model system to study fungal biology, since there are well-developed biological and genetic tools already developed that allow for detailed experimentation.

Huberman's lab has collaborated with Eric Dufresne, professor in the Department of Materials Science and Engineering in the Cornell Duffield College of Engineering, to develop microscopy chambers that allow them to manipulate a change in the concentrations of chemical elements and then watch how N. crassa behaves and grows.

"We're trying to determine how cells are choosing their best nutrient," Huberman said. She will be investigating two hypotheses: whether cells are using their receptors and signaling cascades to detect nutrients right at their tips, across very short distances of five or 10 microns of space; or whether they are able to integrate information across much longer distances of hundreds of microns.

For her grant, Feaga will investigate whether bacteria cells communicate with other bacteria to protect themselves when ribosomes, their protein-making machinery, stall due to stress.

Ribosomes translate mRNA, which are genetic instructions from DNA for making proteins. Under stress (defined as the cell's response to demands or challenges), however, mRNA can get damaged and ribosomes become stalled. Feaga's lab has identified an exporter - a channel going from inside to outside the cell - whose expression increases when ribosomes are stressed.

"The biggest goal of this grant is to figure out what that exporter secretes," Feaga said. "We assume that these molecules can then go and talk to other cells, so we'd like to figure out what those molecules are."

The research could shed light on antibiotic resistance, because many antibiotics stall ribosomes. At the same time, antibiotics only target actively growing cells.

"One way a cell can save itself from antibiotics is if it stops growing, it can allow it to persist through antibiotic treatment," Feaga said. The molecules secreted by stressed bacteria may offer a warning to others. "If a cell is experiencing antibiotic treatment, it may want to warn other cells, 'hey, why don't you stop growing so that way you can survive this treatment.'"

If identified, exporter molecules could potentially be targeted with a drug that blocks them, rendering antibiotics more effective. The mechanism may also apply to other processes associated with bacterial pathogens.

The funds are important because there are many unknowns in trying to identify exporter molecules and large funding agencies like the National Institutes of Health require more data and certainty before they will support a project.

"It's a high-risk project," Feaga said. "We need to know what those molecules are, we just have no idea yet, so these funds are really important to us, because this is a new direction for my lab."