Abstracts - March Seminar
Title: 3D Culturing to Model Kidney Regeneration using Human Induced Pluripotent Stem Cells and Extracellular Matrix Scaffolds Derived from Porcine Kidney
Presenter: Tonya B Bongolan
According to the Kidney Foundation of Canada, 1 in 10 Canadians have kidney disease, with 15 people diagnosed with kidney failure each day. Although dialysis is an available treatment, it costs on average $92,000 per patient per year, making it one of the most expensive health care treatments. While transplantation is the gold standard to treat kidney failure, there is a scarcity in viable organs for transplantation, and so 76% of patients on the waitlist for organ transplantation are specifically waiting for a kidney. Thus, there is an urgent need for novel therapeutics to treat kidney failure. Research in the field of regenerative medicine has made major advancements in the regeneration of whole organs for transplantation using biomaterials. Specifically, we aim to differentiate stem cells into kidney progenitor cells, decellularize porcine kidneys to obtain extracellular matrix (ECM) scaffolds, and recellularize scaffolds to regenerate a kidney suitable for human transplantation. An ECM scaffold would provide the complex microarchitecture normally found in the kidney, complete with specific proteins, glycosaminoglycans and growth factors. This would create a renal progenitor niche in which cells can survive, proliferate, and differentiate into mature kidney cells. While this technology has been used to regenerate other organs in lower mammal species such as the liver, lung, and pancreas, there is limited knowledge of the ECM factors necessary for proper patterning and function following recellularization in the kidney specifically. With a main focus on whole kidney regeneration, we aim to understand cell-ECM interactions that direct stem cell differentiation.
Title: The temporal expression patterns of CREB governing long-term memory formation
Presenter: Albert Park
Centuries of investigation related to learning has wondered why certain life experiences are encoded as memories, while others are not encoded as memories. In the mammalian nervous system, the formation of long-term memories in the brain are regulated by a stunningly complex interaction of molecular effectors. In particular, the cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) is a nodal transcription factor that has been hypothesized to be a molecular switch governing the formation of long-term memories in the mammalian brain. The present thesis takes advantage of a novel optogenetic regulator of CREB, applying it for the first time in an in vivo system, to present the first evidence showing that a temporally-restricted elevation in CREB function, in a small proportion of neurons in the lateral amygdala (LA), is sufficient to enhance the encoding of long-term memories in a living mouse. Specifically, a restricted spike in CREB function one hour before, but not immediately before nor immediately after, learning in a small proportion of LA neurons is sufficient to enhance the encoding of an auditory fear memory. This behavioural result is highly consistent with behavioural results generated by enhancing CREB directly in a small proportion of LA neurons through temporally imprecise, virally-delivered overexpression. These results, in combination with the existing literature, suggest that the timing of variations in endogenous CREB function govern the formation or forgetting of long-term memories.