In the Monaco lab, our primary goal is the identification and characterisation of genes that cause susceptibility to childhood disorders of the brain. At the moment, we have active projects investigating autism, dyslexia (or reading impairment), language impairment and Menkes disease.
Autism, language impairment and dyslexia are all complex genetic disorders (these are also sometimes called multifactorial or polygenic disorders). This means that although they run in families, they are not simply inherited. Instead, they involve several normal genetic variants and can also be affected by environmental influences. Certain combinations of these variants, when accompanied by a particular environment, make some individuals particularly sensitive to the onset of disorder. The involvement of many different genes and the fact that the combinations of risk variants may differ between affected individuals mean that genes for complex disorders are particularly hard to detect. Nonetheless, recent advances in genetics and technology have helped this process and contributory genes are starting to be identified. Through our research, we have identified genes that play a role in susceptibility to dyslexia (KIAA0319), autism (MET, SHANK3 and DOCK4) and language impairment (CNTNAP2). In our current research, we are continuing the process of gene identification whilst characterising the role of recently identified variants. We are also investigating how risk variants might interact with environmental factors to cause disorder. We would like to find out what these genes do during brain development and how genetic variations make some people more susceptible to developmental disorders than others. It is important to note that because of the complexity of these disorders, we will probably never be able to accurately predict which people are likely to develop them and it is unlikely that we will be able to cure them. Instead, we hope that by identifying the genes, biological pathways and brain regions important for these disorders, we will be able to better understand what causes them. This in turn will help to develop better diagnosis and treatments for affected individuals and families.
In contrast to the above disorders, Menkes disease is always caused by a change in the genetic sequence of a single gene. This change is known as a mutation and prevents the gene from doing its intended job. In the case of the Menkes gene (known as ATP7A), this job is to make a protein that helps cells to process copper. Individuals with Menkes disease cannot properly absorb copper into their cells and this severely affects their development. Most patients with Menkes Disease die within the first decade of their life. Our current research is looking at how the Menkes protein transports copper around the cell. We hope that by better understanding the way in which cells transport copper, it will be possible to develop new treatments that will help individuals affected by this disease.
For more information about each of our research areas, please follow the links to the project pages.