Brain Star - July 1, 2003 - Biosketch

Name:
Martina Metzler

My interest to pursue a career in biological sciences started early in school and was strongly encouraged by my family and University teachers. After completion of my Diploma in Biology at the University of Fribourg in Switzerland, I moved to Zürich to undertake graduate studies in the laboratory of Dr. Michel Aguet in the Department of Immunology and Virology (1987-1991). With my thesis work, I analysed the signal transduction of the human-interferon receptor (gamma-IFNR) and was able to identify a cytoplasmic receptor epitope, containing a phosphorylation site that blocked gamma-interferon induced response pathways using antibody microinjection techniques. Subsequently, I decided to go abroad for postdoctoral studies and I was specifically looking for a research environment that allowed me to continue my scientific career in a multidisciplinary environment. I found such an environment at the Biomedical Research Centre at the University of British Columbia where research was focused on the analysis of cytokine function and hematopoiesis. There, I joined the laboratory of Dr. Jamey Marth, where I generated Mgat-1 knock-out mice and studied the role of N-linked carbohydrates on mouse development and hematopoiesis. Through my participation in the Canadian Genetics Disease Network I became more and more interested in understanding disease mechanisms that underlie pathologic human conditions. I decided to join Dr. Michael Hayden's laboratory to apply my expertise in gene targeting and the analysis of gene function to study the neurodegenerative disorder Huntington's Disease (HD). In order to elucidate the molecular mechanism of this disease, which is caused by polyglutamine expansion in huntingtin, I decided to focus my research on the analysis of huntingtin function and the function of huntingtin interacting proteins (HIPs) whose association with mutant huntingtin is altered in HD. I discovered that huntingtin is required for expansion of several progenitor cell lineages in vitro but its exact function, in particular in the CNS, remained elusive. In contrast, studies of huntingtin interacting proteins, in particular HIP1, proofed to be more informative. Through collaboration with the laboratory of Dr. Peter McPherson we have shown that HIP1 and its family member HIP12 functions in clathrin-mediated endocytosis in vitro. Currently, I am focusing my research on the characterization of HIP1 knock-out mice to investigate HIP1 function in vivo, and the role of huntingtin in intracellular transport in vitro. My future goal is to pursue an independent academic research career to study alterations in intracellular transport and their contribution to the development of human diseases