Machine learning of evolutionary forces within families using single-cell sequencing
Are you different from your brothers and sisters but have the same parents? Why is it that two parents can create children that are genetically unique? The answer is meiosis. We are seeking an enthusiastic bioinformatician or scientist with an interest in genetics and evolution, to uncover how DNA repair pathways regulate generation of diversity during meiosis.
In our bodies, DNA double-strand breaks are incredibly dangerous and must be repaired. Nonetheless, there are natural processes that actively generate DNA double strand breaks in their hundreds during meiosis, to allow genetic recombination, or the reshuffling of genetic material between related chromosomes. This process is tightly regulated by mechanisms that are widely conserved in eukaryotes. We previously showed that mutants of the gene FANCM cause a huge increase in meiotic recombination in plants (eg Crismani et al, Science 2012). A related gene has the same effect in yeast. We have now generated FANCM-deficient mice to determine if the same process governs genetic diversity in mammals.
This research has potential implications for our understanding and treatment of infertility in humans. Your project will take place in a dynamic young team of experts skilled in genetics and single-cell genomics. You will learn and use a diverse set of bioinformatics techniques, which span; single cell sequencing, next generation bulk sequence analysis, haplotype analysis, analysis of recombination frequencies, mouse genetics and general analysis of meiosis.
This project will see you develop significant computational novelty, and will work towards uncovering how the generation of genetic diversity is regulated, and potentially affected in human disease such as certain types of infertility. If there is a strong desire to do so, the project may be adapted to include some wet-lab experiments.
Dr Wayne Crismani
Dr Davis McCarthy
DNA repair & recombination
For further information about this project, contact: