An interdisciplinary team of Caltech researchers has received an NIH Director's Transformative Research Award from the National Institutes of Health's High-Risk, High-Reward Research Program. The grant is part of the NIH Common Fund, which supports high-impact programs across NIH institutes and centers. The Transformative Research Award, established in 2009, promotes cross-cutting, interdisciplinary approaches and is open to individuals and teams of investigators who propose research that could potentially create or challenge existing paradigms.
Co-principal investigators on the award are Michael Elowitz, the Roscoe Gilkey Dickinson Professor of Biology and Bioengineering and Howard Hughes Medical Institute Investigator; Lior Pachter (BS '94), Bren Professor of Computational Biology and Computing and Mathematical Sciences; Carlos Lois, research professor of biology; and Rong Lu of USC. Elowitz, Pachter, and Lois are affiliated faculty members with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.
With the grant, the team plans to introduce imaging and recording technologies to directly visualize and understand the process through which blood and immune cells are generated and committed into specific fates within bone marrow. To do this, they will combine spatial transcriptomics and an engineered recording system called MEMOIR (Memory by Engineered Mutagenesis with Optical In situ Readout) to pinpoint where different cell types reside in the bone marrow, how they are related to one another, and how they interact.
Research in Elowitz's lab focuses on understanding how to build biological circuits. As cells replicate, differentiate, communicate, and develop, they can be thought of as living devices. Elowitz and his team analyze how cells effectively use molecular and cellular circuits in order to design synthetic circuits that can provide useful new cellular capacities. The lab combines approaches from systems biology and synthetic biology to understand cellular behaviors and then design solutions to biomedical challenges. His research has recently modeled how cells differentiate to choose their fates using synthetic gene circuits.
Pachter is a computational biologist who develops computational and experimental methods for use in genomics. He has contributed to areas of research such as comparative genomics, as well as to sequencing efforts for mouse, rat, chicken, and fly genomes, and to the pilot phase of the ENCODE project-an effort to build a comprehensive list of functional elements in the human genome.
More recently, he has focused on functional genomics, which seeks to answer questions about the function and interaction of DNA, RNA, and protein products. In 2021, his laboratory developed a software tool that enables the quick processing of large sets of genomic data in about 30 minutes using the computing power of an average laptop. His work has also contributed techniques to map millions of cells in the mouse brain.
The Lois lab investigates the mechanisms by which the coordinated activity of neurons connected to each other in circuits gives rise to brain function. His team focuses on three major questions: What is the wiring diagram of the connections that link neurons together in a circuit? How does information flow through a neuronal circuit? And how does the function of brain circuits remain reliable despite noise? To answer these questions, Lois's team is developing new genetic technologies to identify neuronal connectivity to manipulate the biophysical properties of neurons and to record their dynamics. His laboratory utilizes model organisms to study processes in the brain such as memory.
