Our lab is interested in the processes that promote new arrangements of genes along our chromosomes. Genes are the basic unit encoding information that the cell needs to make specific proteins such as enzymes and are arranged linearly along chromosomes of which human contain 23 pairs and budding yeast 16. Rearrangements of gene can be both beneficial as well as detrimental to the organism and are thus tightly regulated by cells- the basic building blocks of our bodies.
An example of beneficial rearrangements occurs during the formation of eggs and sperm- a process termed meiosis. Proteins that promote rearrangements ensure that the genes that we have inherited from our parents are mixed up before we pass them on to our children. We all inherit two copies or versions of each gene (termed alleles) as well as chromosomes; one from each of our parents. The chromosomes are broken into many pieces during meiosis and combined (or 'recombined') back into harlequin chromosomes that now contain information from both parental chromosomes. Thus, new combinations of gene versions are passed on. This process is also termed 'crossing over' and is so conserved in evolution that many of the proteins that carry out these functions are found in the humble bread-baking yeast (budding yeast) as well as human and plants.
Besides generating new combinations of genes that we pass on, crossover promoting proteins also ensure that all of our 23 pairs of chromosomes find each other during the cell division process. We have all inherited 23 pairs of chromosomes; one of each pair from our parents ('one chromosome complement'). In turn, to make sure that future generations inherit only 23 chromosomes from each parent, egg and sperm formation involves halfing the chromosome number, otherwise our children would end up with 92 chromosomes and their children 184, etc.. However, halfing the number must not be random as egg and sperm must each pass on exactly one chromosome from each pair. By forming the attachments between chromosomes belonging to the same pair, crossover promoting proteins ensure their correct pairing. When this process goes wrong, chromosome number abnormalities such as Down's Syndrome/Trisomy 21 as well as infertility are the results.
Finally, the cells that do not give rise to egg and sperm suppress the activity of crossover promoting proteins. In the majority of cells in our bodies, rearrangements of genes and the formation of harlequin chromosomes is a sign of instability that may lead to cancer. We are trying to understand how and why that is.
Our research work is funded by:
