Summer Undergraduate Research Program
Faculty Project Proposal Submission
Project Submission deadline: February 14, 2014
Faculty Name: Katja Brückner
Email:
Phone Number: 415 476 3827
Department/Organization Affiliation: University of California San Francisco (UCSF)/ Broad Center; Cell and Tissue Biology; Anatomy; Cardiovascular Research Institute (CVRI)
Preferred Method of Contact: email
Project Name(s): How neurons talk to the blood: Sensory regulation of hematopoiesis in a Drosophila model
General Topic (Keywords): microenvironment, niche, stem cell, sensory stimulus, peripheral nervous system, blood cell, hematopoiesis, menthol, wasabi, Drosophila, genetics, cell proliferation, cell adhesion, adaptation, calcium signaling, Trp channels
Project Description(s):
One of the outstanding questions in animal development and tissue homeostasis is how extrinsic sensory stimuli regulate signaling cascades and biological responses in stem cell niches and tissue microenvironments that lead to adaptation. Our lab addresses this question using the fruitfly Drosophila melanogaster as a model. During Drosophila larval development, the majority of blood cells (hemocytes) reside in direct contact with segmentally repeated peripheral nervous system (PNS) sensory neuron clusters. Hemocytes require the PNS for their proliferation, survival and recruitment to these specialized microenvironments, known as Hematopoietic Pockets (HPs) (Makhijani et al. Development 2011). Recently, the Brückner lab identified PNS neuron-produced Activinβ as a key regulator of hemocyte adhesion and proliferation, demonstrating that signals from the PNS determine blood cell responses (Makhijani et al.). Additionally, the lab gained evidence that blood cell responses also depend on sensory neuron activity, which we can trigger by exposing larvae to the plant stimulants menthol (mint) or AITC (allyl isothiocyanate), a compound of wasabi. Using GCaMP6 calcium imaging, we found that menthol or AITC induce a rapid increase of intracellular calcium (Ca2+) in both PNS neurons and, subsequently, in hemocytes, consistent with an activation of Trp (Transient receptor potential) channels that mediate cation influx and membrane depolarization. Based on these findings, we hypothesize that PNS neurons signal directly to hemocytes, and that blood cell recruitment and homeostasis are regulated by neuronal electrochemical activity. In this summer project, we want to dissect the mechanism by which menthol and AITC trigger blood cell responses and adaptation, using optogenetic and other inducible neurobiology tools, GCaMP6 live calcium imaging, and Drosophila genetics.
Desired Skills or Experience: We are looking for a talented and enthusiastic student with some lab experience; experience in Drosophila is preferred but not necessary.
Time Commitment: open for discussion
Preferred Starting Date: open for discussion