Abstract
Jolly, Lachlan PhD
PhD awarded 2010, Boichemistry, The University of Adelaide and Women’s and Children’s Health Research Institute & Grant Funded Scientist – Neurogenetics Research Program, SA Pathology
Understanding molecular basis of learning and memory problems
On average about 1/50 individuals world-wide suffer from learning and memory problems. Diagnosed during childhood, and collectively known as intellectual disabilities (ID), these problems are the common outcome of a collection of hundreds of disorders encompassing a wide range of central nervous systems defects. Significantly, the diagnosis of ID has ongoing clinical relevance, with patients suffering a continued reduction in their qualities of life. Genetic/DNA defects commonly cause ID. The identification of these genetic defects is thus of significant medical importance. We have recently discovered mutations in a gene called USP9X are responsible for a heritable form of ID.
In our research, we embarked on identifying how USP9X mutations actually lead to ID in human patients by modelling the disease in mice. Using sophisticated methods we manipulated Usp9x gene activity in cells of a developing mouse brain. Specifically we looked at two types of brain cells, namely (1) nerve stem cells, which are responsible for embryonic stages of brain growth, and (2) maturing nerve cells, which will ultimately be responsible for the transmission of information throughout the entire brain. Through our experiments we have learned that USP9X activity needs to be tightly controlled to ensure both proper embryonic brain growth and the generation of functional brain circuitry. Together, this information has opened the door to resolving the pathological mechanisms behind ID. This knowledge of molecular mechanisms is critical not only for future design of therapeutic strategies to help these patients, but also for enhancing our knowledge of how brain works.