Dr Mark Bailey
Research by my group focuses on four main areas, the molecular genetics of complex inherited neurological disorders, the genetics of complex normal traits and their relation to disease risk, the molecular biology of neuronal regeneration and the evolution of gene families involved in brain function and development.
We are studying two inherited neurological disorders of the brain, Rett syndrome and idiopathic epilepsy, and one disorder of the inner ear, Ménière's disease.
Rett Syndrome (RS)
Rett Syndrome is a severe developmental disorder in which the pathology is almost exclusively limited to the brain, and which affects only girls, leaving them severely underdeveloped, cognitively, and with related health problems. It is caused in most cases by sporadic mutations in MECP2, a gene that encodes a protein that participates in epigenetic regulation of genome function and gene expression. We are interested in two aspects of the molecular pathology. Firstly, the relationship between genotype (what mutation is carried, and in what gene) and phenotype (what are the clinical symptoms and natural history of the disorder in the individual patient); and secondly, how the downstream events in the causal pathway leading to the clinical disorder come to disrupt neuronal functioning and network behaviour. Ongoing work includes screening patients for mutations and other variants in MECP2 and establishment of cultured tissue models in which to investigate neurophysiological changes in RS. We have established collaborations with several clinicians, geneticists, neuroscientists (including Dr Stuart Cobb in the Institute of Neuroscience & Psychology, MVLS) and statisticians in the UK and Europe and are currently engaged in the largest genotype-phenotype correlation study of its kind.
Idiopathic Epilepsy (IE)
The term idiopathic epilepsy covers a number of different syndromes in which repeated, spontaneous seizures are exhibited. IE is complex and complicated - more than one gene can predispose to the same epilepsy subtype, and genes that predispose to more than one epilepsy subtype exist, leading to the clustering of complex mixtures of epilepsies within families. We are attempting to identify genes that cause presidposition to various IE subtypes, either in families or sporadic cases, including idiopathic generalised epilepsy (IGE), juvenile myoclonic epilepsy (JME), generalised epilepsy with febrile seizures plus other seizures ('GEFS+') and 'unclassified' epilepsies. We have collaborations with clinicians including Dr Sameer Zuberi (Royal Hospital for Sick Children, Glasgow) and Prof Martin Brodie and Dr Graeme Sills (Western Infirmary, Glasgow).
Ménière's disease (MD)
Ménière's disease affects about 1/2000 people, mostly sporadically, and generally manifests as disorienting and incapacitating episodes of vertigo, tinnitus and hearing loss. We are working with Mr Gavin Morrison, whose father, Andrew, collected a unique set of rarely identified multiply affected Ménière's families. We have mapped a gene predisposing to familial MD in these families and are currently trying to identify the genetic lesion underlying the disease. We are also planning a larger study aimed at identifying predisposing gene variants in patients with sporadic MD.
All these project areas will contribute to our understanding of important disorders at the molecular and genetic level, and to knowledge of the genetic disease burden in the UK population.
Genetics of normal traits and disease risk
I am working with Dr Richard Wilson (now retired, MVLS) and Dr Yannis Pitsiladis (the Institute of Cardiovascular & Medical Sciences, MVLS)) to investigate the effect that genes have on body composition and performance phenotypes in the normal population, and the interaction of such genes with environmental factors. We are interested particularly in the genes influencing adiposity (and may also have a role in predisposition to obesity) and how their influence is modulated by dietary factors and exercise in children, adolescents and adults. Thus far, our analyses have helped to provide an understanding of the roles of such genes as ACE, ADRB2 and ACTN3 in influencing adiposity and performance, and further work is planned with other genes and other population samples. Recently, I have developed a collaboration with another member of the Institute of Cardiovascular & Medical Sciences, Dr Jason Gill, to investigate the complex genetic and environmental influences on obesity and type 2 diabetes in different ethnic groups in South America, in collaboration with academics in Chile.
In collaboration with Dr John Riddell, Institute of Neuroscience & Psychology, MVLS, we are currently investigating the molecular events underlying successful and failed, or blocked, regeneration of peripheral sensory neurons after injury using a gene microarray approach.
Evolution of gene families involved in brain function and development
We have been studying the evolution of brain gene families, particularly that encoding members of the type A receptor for the neurotransmitter, GABA (GABAA receptors), and what the phylogenomics of such families can tell us about the history of genome evolution in chordates - in particular whether there is evidence for a series of genome duplications early in chordate evolution that can help explain the dominance of this group and the extreme importance of the brain in vertebrates. This has involved gene cloning and bioinformatic/phylogenomic/phylogenetic approaches to investigate when any possible expansions in gene number occurred and their implications. There is also the hope that an understanding of the evolutionary relationships between gene family members will help us in the analysis and prediction of their functional attributes. This information might one day be used in the rational design of new drugs for conditions such as epilepsy, anxiety and many others.
We are also engaged in research into human-computer interactions and automation of dataflows in molecular biology. We have developed a JAVA-based tool for performing BLAST searches, managing their output and creating persistent sequence sets for downstream analysis using a database system. Automation of experimental data recording and the potential for integrating computing support for lab-based activities are also being investigated.