Since its announcement in 2018, there has been an overwhelming response to the BRIA initiative. In 2019, of 25 submitted letters of intent, 7 projects were recommended for submission as full proposals, and of these, 3 have been funded.
A fundamental question in eukaryotic biology is how organisms transmit their genomes—shuffled but undamaged—across sexual generations. Homologous recombination during meiosis plays a central role in this genetic transmission, but despite over a century of study the underlying molecular mechanisms remain poorly understood because of a paucity of biochemical and structural information. This project will tackle this longstanding challenge by bringing together two labs with complementary expertise in meiotic recombination (Keeney) and structural biology (Patel). These groups will study how recombination-promoting proteins work by combining biochemical and structural studies of purified proteins with novel genetic and cell biology experiments in baker’s yeast and in mice.
Probing the role of inflammatory fatty acid metabolism in innate immune memory formation
The project studies how leukocytes, which make the first line of our immune defenses against invading microorganisms, can “remember” past challenges, such as tissue injury and infection, to respond more aggressively to alike challenges in the future. By combining intravital imaging of antimicrobial leukocyte responses in intact zebrafish larvae with current genetic and epigenetic techniques, we seek to unravel the cellular and metabolic basis of “innate immune memory” formation in a developing vertebrate, whose antibody-based, adaptive immune mechanisms have not yet become operant. The expected insights could open new avenues for modulating leukocyte responses for therapeutic advantage during inflammatory diseases and cancer.
Molecular indexing of chromatin
The overall goal of this research project is to develop new methodology to identify proteins and DNA that interact in 3-dimensional space. Our technology relies on new methods that allow us to uniquely tag and then identify interacting molecules within a population of billions. We will use this new methodology to address fundamental unanswered questions in the transcription and genome integrity fields: we focus on RNA Polymerase II and aim to learn how transcription is regulated in the context of chromatin and how transcription may interfere with DNA replication. Our method is novel, does not require specialized equipment, and can be readily adapted to study any protein that interacts with the genome.
We expect there to be two calls for BRIA pilot projects, and one call for full applications each year. Revisions of projects will be considered as new submissions.