Research Project
7696558
DESCRIPTION (provided by applicant): Recombination is a crucial part of sexual reproduction, occurring in plants and animals including humans. If recombination malfunctions, sex cells (sperm and eggs for example) do not receive the correct chromosome complement to pass to the next generation. Recombination also generates diversity by allowing genetic variation present in the parents to be rearranged in their offspring. Many genes involved in recombination also have a role in genome maintenance during growth and development, so mutations in recombination genes often have devastating effects. Not only may inheritance be disturbed, resulting in infertility, generation of additional mutations and potential genetic disease but, since the stability of the genome is no longer ensured, such mutations may lead to uncontrolled cellular growth, known as cancer. Most of what is known about meiotic recombination derives from elegant studies using the budding yeast Saccharomyces cerevisiae. Many of these types of study have not been done in other organisms as recombination is much less frequent than in yeast, making the amount of work required to collect useful information prohibitive. The specific aim of this application is the development of an assay that uses fluorescent proteins to identify recombinant offspring, making it much less labour intensive to obtain informative recombination data. Use of this assay will make it possible to carry out a detailed analysis of recombination in the fungus Neurospora crassa, an organism with a more complex lifestyle and genome than yeast. Such study will assist in understanding which aspects of meiotic recombination vary between organisms and which are constant, contributing to a full description of recombination in human beings. This will ultimately assist in design of new screening programs for inherited diseases and for susceptibility to cancer, and will improve predictions of the long-term consequences of genetic modifications to crop plants and transgene-based therapies for human disease. The proposed work is peculiarly suitable for carrying out in my laboratory in Adelaide. I have been working on the mechanisms and regulation of meiotic recombination for the past several decades using the Neurospora model system, accumulating the extensive range of genetic materials, tools and experience needed to conduct the proposed work which would be extremely difficult, time consuming and inordinately expensive for another laboratory to take up. Accordingly, conduct of the work is dependent on funding being made available for conduct of the work in Australia. PUBLIC HEALTH RELEVANCE: Recombination, which occurs in all sexually reproducing organisms, generates genetic diversity and ensures that gametes receive the correct number of chromosomes. It is difficult to study in many organisms as each specific genomic location experiences recombination only occasionally. Use of the proposed system will increase understanding of recombination pathways and the genes involved in the process, adding to knowledge in the areas of human reproduction, genetic disease and cancer etiology.
