Innovation gets a boost from 2023 Koda-Kimble Seed Awards

Four projects that have the potential to move forward the mission of the UCSF School of Pharmacy in new ways earned the 2023 Mary Anne Koda-Kimble Seed Award for Innovation this spring. The Seed Awards intend to fuel endeavors for which there is no ready or traditional source of funding, and this is the ninth year of awards.

This year’s awards will help fund research on immune system behavior, library generation of genotype-phenotype maps, quantitative nucleic acid measurements, and allosteric coupling.

Mary Anne Koda-Kimble, PharmD, was the School’s dean from 1998 to 2012 and is known worldwide as the coeditor of the first patient-centered, therapeutics-focused textbook for schools of pharmacy. The Seed Award for Innovation honors her legacy and was announced in 2012 with a $1 million endowment from the Joseph and Vera Long Foundation, a legacy of Joseph M. Long, cofounder of Longs Drug Stores, and his wife Vera, a strong supporter of health and education.

The winning projects, spearheaded by students, postdocs, and faculty members in the School, will share about $65,000 in total funding.

Hijacking of a mammalian self-recognition receptor by a poxvirus

Principal applicant: Balyn Zaro, PhD, assistant professor, Department of Pharmaceutical Chemistry.

The project: How does the immune system recognize and avoid attacking its own cells? Zaro will investigate myxoma virus, which encodes a protein—M128L—that resembles a molecule found on normal cells, to determine if M128L tricks the immune system by interacting with a receptor—SIRPα—on immune cells, preventing them from attacking the infected cells. If confirmed, this would be the first time these interactions are demonstrated. The research could provide important insights into virus behavior and the immune response.

Massively combinatorial library generation for transformative pharmacogenomics

Principal applicant: Christian Macdonald, PhD, postdoctoral scholar, Fraser Lab, Department of Bioengineering and Therapeutic Sciences.

The project: How do different genotypes give rise to phenotypes? Macdonald will investigate an approach that offers an exponential increase in our ability to produce complex genotype-phenotype maps using high-throughput measurements, hoping it will allow unprecedented insight into clinical variants as well as fundamental biophysics. This improves upon a previously published approach using oligo pools called DIMPLE which has demonstrated its value for functional and folding assays in potassium channels and drug transporters. The team will test their strategy with OCT1, an important transporter mediating the metabolism of a broad range of substances, including major cancer, diabetes, and antibiotic compounds.

Shaken droplet digital LAMP: a simplified and rapid diagnostic for point-of-care quantification of viral titers

Principal applicant: Daniel Weisgerber, PhD, postdoctoral researcher, Abate Lab, Department of Bioengineering and Therapeutic Sciences.

The project: Can we increase access and speed of HIV testing? Weisgerber proposes developing shaken droplet digital loop-mediated isothermal amplification (sddLAMP) to advance quantitative nucleic acid measurements to point-of-care and at-home environments. Shaken emulsification is a microfluidic-free method that requires neither special training nor special equipment. Emulsions are generated by agitation of a sample in the presence of an appropriately formulated oil. A smartphone will measure and analyze the sample via a novel, dual-layered viewing chamber designed to count droplets’ reactions. The project could help reduce infections of not just HIV but, with further study, also other viral targets, both locally and worldwide.

Dissection of allostery in Ras GTPases using high-throughput biochemistry and machine learning

Principal applicant: Jonathan Zhang, Biophysics graduate student, Kortemme and Pinney Labs, Department of Bioengineering and Therapeutic Sciences.

The project: This research proposal aims to identify the molecular mechanisms for how allostery regulates the function of Ras GTPases, a family of proteins that coordinate diverse cellular functions. By integrating high-throughput enzymology and machine learning, the study will explore how molecular perturbations at GTPase regulatory sites affect the biochemical activity of these proteins. Zhang’s project could pave the way for new targeted drug development and the engineering of GTPases, addressing outstanding challenges in synthetic and systems biology, as well as medicine.