UCSF/ Broad Center; Cell & Tissue Biology; CVRI
Cell signaling, developmental & stem cell biology, hematopoiesis, nervous system, microenvironment, Drosophila, oxygen sensing, sensory neurons, transdifferentiation, blood cell, tissue macrophage, adaptation, neuronal channels, calcium signaling, activin signaling, transcription factors, scRNAseq
How is neuronal sensing linked to organ and tissue development? How do specialized cells transdifferentiate, bypassing the need for stem or progenitor cells? Our lab addresses these questions studying a model of hematopoiesis in the fruitfly Drosophila melanogaster. In the Drosophila larva, developing blood cells are in direct contact with segmentally repeated sensory neuron clusters of the peripheral nervous system. Blood cells require sensory neurons for their proliferation, survival and transdifferentiation in these specialized microenvironments, known as Hematopoietic Pockets (HPs) (Makhijani et al. Development 2011; Gold and Brückner Seminars in Immunology 2015; Makhijani et al. Nature Communications 2017; Corcoran et al. in preparation). Hematopoiesis in the larva is crucial for the blood cell system in the adult animal (Sanchez Bosch et al. Dev Cell 2019). In this summer project, we focus on transdifferentiation between two blood cell types in this model, from macrophage-like plasmatocytes into crystal cells that execute melanization. Blood cell transdifferentiation is known in vertebrates and many other species across the animal kingdom, but its regulation in vivo remains poorly understood. We investigate the Drosophila in vivo transdifferentiation paradigm to understand how oxygen sensing activates specific neuron populations that in turn signal to promote blood cell transdifferentiation. Using Drosophila genetics, RNAi, and cell based assays, we dissect (1) oxygen-induced signaling steps in sensory neurons, (2) activation of signaling pathways in blood cells following stimulation by signals from sensory neurons, and (3) transcription factors that drive the fate change from plasmatocytes to crystal cells, based on scRNAseq data. This work reveals how oxygen sensing, through sensory neurons and their activity, regulates blood cell transdifferentiation in vivo, suggesting similar principles in other species.
We are looking for talented and enthusiastic students with some previous lab experience; experience with Drosophila is preferred.
Expected time commitment
Full time during the summer; continuation during the school year and future paid position possible.
Preferred start time: