Dr Gai McMichael

Gai McMichael currently works with Prof Mark Boyd, Chair of Medicine at the Lyell McEwin Hospital. My role as research coordinator sees me working on several projects and concepts, including areas of infectious and chronic diseases and specifically how social determinants of health, i.e. those conditions in which people are born, grow, work, live, and age, and the wider set of forces and systems that shape the conditions of daily life, impact on health and health outcomes. Poor health outcomes have been extensively documented for individuals experiencing adverse social determinants of health. There is a clear gradient of increasing mortality and worse health outcomes in socioeconomic disadvantage areas. The Northern Area Local Health Network services a relatively disadvantaged and marginalised community. We are interested in research that will provide a better understanding of social and economic conditions that lead to adverse health outcomes, thereby facilitating appropriate measures for early interventions to identify people at risk to have adverse health outcomes. Ultimately we postulate that a better understanding of a persons daily circumstances and appropriate early interventions are likely to lead to better patient health outcomes.

RESEARCH ACHIEVEMENTS
My doctoral research was the first to explore the genetic contribution to cerebral palsy (CP) using whole-exome sequencing (WES) in a cohort of sporadic CP cases. I took an unbiased WES approach to identify potential pathogenic variants for CP in two groups of individuals with CP: sporadic cases (no previous family history of CP) and families with more than one individual with a confirmed diagnosis of CP. In total, 14% of CP cases, by strict criteria, had a potentially disease-causing gene variant. This is significantly higher than 2% previously reported. A further 44% of CP cases had candidate variants that are yet to be resolved in regard to their contribution to CP. Our overall findings suggest for the first time that CP is genetically heterogeneous, involving mutations, mainly de novo, in previously known neurodevelopmental genes and novel candidate CP genes. This work carried out in collaboration with Prof Richard Gibbs, Baylor College of Medicine (BMC) was a collaborative CP research project (in excess of US$1M) of which I was a key initiator. I was invited to work at BCM as
a Research Fellow for part of my PhD project, which resulted in three first author publications, including my seminal paper published in the highly ranked journal of Molecular Psychiatry (2015). My work has had a significant impact, in the medical and scientific community and is radically changing the understanding of CP causation.

Prior to my PhD I completed a Masters degree in Medical Science examining the contribution of copy number variants (CNVs) to CP. Identification of CNVs has provided new insights into human disease. My primary research focus was to investigate the contribution of heritable and de novo CNVs in CP using array comparative genome hybridization. This was a novel study and identified 20% of cases with a rare CNV potentially relevant to CP. Work on this project was conducted in collaboration with Prof Evan Eichler, Washington State, and Prof Christa Martin, Georgia, resulting in a first-author publication in the European Journal of Human Genetics.

My background prior to my role in CP research was in plant science genetics, specifically constructing high-density genetic maps and QTL analysis of disease resistance traits in new barley crop varieties. This role provided me with extensive experience with SNP and microarray methodologies resulting in three publications, which are still highly cited and have had a major impact on plant breeding programs.