Optogenetic Regulation of Insulin Secretion in Pancreatic β-Cells

by Leah Truskinovsky

mentor: Emmanuel Tzanakakis; funding source: Provost’s office

Diabetes is linked to irregular levels of insulin, a hormone which controls blood glucose. Daily insulin injections are inconvenient and ineffective in preventing the long-term complications of diabetes. Recent research showed that pancreatic β-cells (the cells responsible for insulin secretion) can be engineered to enhance their insulin secretion with light. The Tzanakakis Research Group seeks to investigate whether such engineered cells can be activated by red light, which could reach cells from outside of the body, paving the way for treatments without drugs and their serious side effects.

bPAC is a photoactivatable adenylyl cyclase, an enzyme that is light-activated and aids in the conversion of ATP in our cells to cyclic adenosine monophosphate (cAMP). cAMP is an integral component of the insulin secretory pathway, and our laboratory’s incorporation of bPAC into pancreatic β-cells, therefore, targets the upregulation of cAMP production. Our current work aims to focus upon a newer form of the photoactivatable adenylyl cyclase, rPAC. rPAC is activated by red light (as opposed to blue light for bPAC) and significantly reduces the number of obstacles and boundaries associated with blue light illumination. rPAC most notably has a higher tissue penetration depth and therefore would not require a bulky light source, and it also requires less energy, significantly simplifying the implementation of engineered pancreatic β-cells. The Tzanakakis Research Group has previously shown the efficacy of bPAC in safely and precisely increasing insulin secretion levels, and the laboratory’s current work aims to further optimize this study using rPAC, allowing for more convenient and effective diabetes treatments.

My Summer Scholars research work involved the in-depth literature investigation of the insulin secretory pathway, beta cell function, and the structure and function of these light-activated engineered cells, bPAC and rPAC. Gathering these aspects, as well as the analysis of current pharmacological agents and our light-activated diabetes treatment method, my project culminated in a collaborative review paper that is anticipated to be published in the near future. I had the invaluable opportunity to work closely with Professor Tzanakakis, the research group’s principal investigator, and Sylvia Chen, a Ph.D. student member of the research group and my mentor. I had the chance to better understand the molecular pathways and biological constructs of the systems we study, as well as explore scientific review paper research and composition.