UC Santa Cruz cholera biofilm team wins Deloitte QB3 Award for Innovation

Nicholas Shikuma, Kelly Peach, and Walter Bray of UC Santa Cruz: voted award winners by the UC campus community. Photo: Shannon Weiman

A team of UC Santa Cruz researchers searching for drugs to fight cholera won the Deloitte QB3 Award for Innovation, presented by representatives of QB3 and Deloitte Thursday, October 27 at a ceremony at UCSF Mission Bay.

The team—graduate students Kelly Peach and Nicholas Shikuma, with research specialist Walter Bray—developed a high-throughput screening method to identify drugs that prevent Vibrio cholerae, the cholera pathogen, from forming biofilms: thin, tough sheets in which bacteria are shielded from antibiotics.

Biofilms are also a source of infection following operations to implant medical devices, and the team’s method could equally be applied to screen for drugs that disrupt other bacteria.

The $10,000 Award for Innovation, given to a graduate student, postdoc, staff scientist, or team working in QB3 laboratories at UC Berkeley, UC Santa Cruz, and UCSF, recognizes research that has the potential to improve human health.

The competition began in June when QB3 faculty nominated 38 candidates. By September, a jury panel drawn from industry, venture capital, academia, and the media had narrowed the field to five. QB3 then invited the entire Berkeley, UCSF, and Santa Cruz campus communities to vote, ‘American Idol’ style, for the ultimate winner. (San Francisco Business Times reporter Ron Leuty covered the competition.) Santa Cruz featured its team in a news article on its website, while on Twitter, the universities (and the Gladstone Institutes) waged a sporadic battle for votes. In the end more than 1500 votes were cast—over half of them for the Santa Cruz team.

In a paper published this year in the journal Molecular Biosystems, the Santa Cruz team explained that biofilms are involved in over 60% of bacterial infections in humans. Bacteria often lie dormant in biofilms, encased in material that protects them from a host’s immune response—or drugs. Most antibiotics target cells that are actively dividing, so bacteria in a biofilm can sit out a course of treatment and emerge later to multiply. Drugs that disrupt biofilms make bacteria more vulnerable. Ideally, disruptors would be used in “cocktails” with antibiotics to kill free-floating bacteria.

Cholera remains a major Third World pathogen; an outbreak following the 2010 earthquake in Haiti sickened half a million and killed over 5,000. Biofilms are crucial to the virulence of V. cholerae, but no therapeutics exist to disrupt them. In a step toward solving this problem, Bray, Peach, Shikuma, and colleagues developed a technique to grow cholera biofilms in 384-well plates, and an automated method that uses fluorescence microscopy to measure how much biofilm is present in each well. Theirs is the first reported technique in the scientific literature to use images to analyze V. cholerae biofilms.

In a demonstration run, from a relatively small library of 3080 compounds, the team identified 29 compounds that disrupt cholera biofilm without killing the cells. The 29 compounds are “leads”—starting points for a company to test and refine into an actual drug therapy through many rounds of screens and clinical trials.

The work brought together scientists in three QB3 labs at UC Santa Cruz: those of Roger Linington, Scott Lokey, and Fitnat Yildiz. Nadine Gassner, currently the grant program administrator at QB3-Santa Cruz, also contributed.

Four other finalists were in the running:

  • Jonathan Galazka, a UC Berkeley graduate student, for engineering a strain of yeast that digests two types of sugar, thus speeding our path to biofuels and improving our access to clean, reliable, and affordable energy sources
  • Patrick Goodwill, PhD , a UC Berkeley research associate, for a magnetic particle imaging technique that could enable real-time angiography without radiation or iodine tracer
  • Ellen Yeh, MD, PhD, a resident fellow at UCSF, for identifying a potential drug target in the malaria parasite
  • Daniel Zwilling, PhD, a postdoc, and Lily Huang, a research assistant, both at UCSF and the Gladstone Institutes, for discovering a potential treatment to slow neural breakdown in Alzheimer’s and Huntington’s diseases.