2012 Fisher Award Winners

Studentship Project Description – Davis Sam

Supervisor: Doug Allan

Nervous system development hinges upon the precise timing of neuronal differentiation from immaturity to full functional maturity. The Allan Lab at the Life Sciences Centre has discovered
a novel form of neuronal differentiation in Drosophila melanogaster, wherein neurons that are
born in the embryo remain developmentally frozen until they are required at metamorphosis (the
insect analog of human puberty) to repurpose neuronal circuits to an adult-type function.
Understanding such mechanisms has strong implications for understanding the progression of
schizophrenia and autism in humans, where neuronal dysfunction emerges during times of
nervous system remodeling in juveniles and around puberty. Davis Sam will be studying the
genetic mechanisms underlying this age-dependent neuronal awakening from their
developmentally-frozen state. This involves investigating specific interactions among three
important gene regulatory proteins within the Drosophila nervous system. Preliminary data has
led to the hypothesis that these proteins form a repressive cascade that blocks maturation of
developmentally-frozen neurons until they are triggered to mature. Such a pathway offers an
ideal mechanism to maintain neurons in an immature state throughout development until they are required by the adult nervous system. These studies will rapidly provide our first molecular
genetic understanding of this novel mechanism for controlling neuronal maturation.


Studentship Project Description – Elaine Xu

Supervisor: Jim Johnson

Age-dependent changes in the morphology of human and mouse pancreatic islets:  Old mice are humans too?

Diabetes is a devastating chronic condition caused by the absolute or relative loss of functional pancreatic islet beta-cells. For decades, relatively young rodents have served as the primary animal models for diabetes research. It has long been noted that islets from young mice form a distinct cellular pattern, with insulin-secreting beta-cells forming the core and glucagon-secreting alpha-cells forming an outer mantle. This architecture is thought to have important functional consequences and is perturbed in diabetes. It should be noted, however, that type 2 diabetes is a disease of aging and very little work has explored the function and makeup of islets from older mice (>1 year) that would approximate adult-onset diabetes. Lately, human pancreas tissue samples and islets have become more widely available for research purposes. Many investigators have reported that human islet architecture is quite different from that reported for rodents. This has caused some to question the relevance of rodent models and suggest different working models for the human islet in health and disease. Preliminary work from the Johnson laboratory, has suggested that old mice can have ‘human-like’ islet organization. Moreover, emerging data from very young human samples showing ‘mouse-like’ islet architecture also suggests the possibility that islet architecture changes as a factor of age, rather than being different between mammalian species. Thus, the goal of the project is to perform a complete and quantitative characterization of islet architecture in mice of different ages, including samples in the Johnson laboratory from almost 2 year old mice, and compare these to human samples in the Johnson laboratory and published in the literature. We will employ quadruple labeling, high-content imaging instruments and powerful software to perform these analyses.  Simultaneously, during the downtimes of the bench experiments, Elaine will perform an exhaustive literature search to examine each publication where mouse and human islets have been compared side by side, noting the age of each, to determine whether significant functional differences really exist.