Using Genetic Buffering Relationships Identified in Fission Yeast to Elucidate the Molecular Pathology of Tuberous Sclerosis
Annual rept. 1 Jul 2014-30 Jun 2015
UNIVERSITY OF WESTERN ONTARIO LONDON
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Using the genetically tractable fission yeast as a model, we sought to exploit recent advances in gene interaction biology to identify novel drug targets for use in the fight against tuberous sclerosis. Our ongoing study has identified two genes, fft3 a SMARCAD1 family ATP-dependent DNA helicase and ypa1 a PTPA family protein phosphatase as excellent candidates for continued analysis. While deletion of either gene has little phenotypic effect in normal cells, their loss in either tsc1 or tsc2 mutants profoundly inhibits growth. Thus, inhibition of either fft3 or ypa1 may represent an Achilles heel of cells defective in hamartin or tuberin function. In addition, due to the fact that our work necessitated the ability to unambiguously compare genetic interactions, we developed a formal and general mathematical framework for the quantitation of genetic buffering strength. This methodology was recently published and is freely available to the public at www.mathematicajournal. com201503the-quantitation-of-non-classical-buffering.
- Medicine and Medical Research