Senior Scientist and Principal Investigator: Mike Forte
The Forte lab is committed to the use of genetics to understand complex biological responses. It has often been said that geneticists, especially following classical training, approach and think about a question in a fundamentally different way than other biomedical scientists. This is undoubtedly true. As a result, the Forte lab believes that the use of mutants, both gain and loss of function, and the epistatic interactions between the various mutant forms result in novel, often unique and unexpected insights into the function of specific proteins and/or pathways that complement and amplify information obtained by other approaches. While this represents the general "philosophical" statement of how we do things, we also recognize that the application of these formalisms alone, and the precision of the information gathered, requires the coordinated use of additional experimental approaches. For example, work on MS, based in the response of a variety of mutant mice to murine models of the disease, has led, in part, to the "mitochondrial hypothesis" of axonal severing responsible for the permanent disability that develops in afflicted individuals. However, the consequences of these mutations on mitochondrial function requires the corresponding application of biochemical tools, novel live-cell imaging techniques, and proteomics to really understand what it is about mitochondria that is critical to the progression of the disease. In our work on axonal guidance in Drosophila, again, initial insights are gathered on the basis of phenotypes present in mutant animals, and extended by analysis of epistatic interactions with other mutants generating similar phenotypes. Yet, the analysis in the fly work is necessarily multidisciplinary as well. Consequently, although we start with mutants and base much of subsequent analysis on the application of genetic principals, we remain open-minded and apply whatever tools necessary to get the right answers.