Transcriptomics and Neurogenetics

Our research sits at the intersection of genomics and neuroscience, utilising a number of genomic approaches (RNA-Seq, long-read sequencing, targeted RNA sequencing and single cell sequencing) to investigate gene expression and function in the human brain and in neuropsychiatric disorders. We are investigating how the expression and splicing of risk genes (both protein coding and noncoding) can change to create disease risk and how detecting these changes can help us understand what causes neuropsychiatric disorders and identify novel treatment targets.

A second interest of our research is to develop and utilise novel sequencing methods. Recently we have focused on Nanopore sequencing, a technology that can sequence both DNA and native RNA. We are very interested applying Nanopore sequencing to many research questions and in developing novel applications for this technology.

Project SupervisorsProjects

Dr Mike Clark

Professor Christine Wells

Project 1: Deciphering the impact of isoform regulation on stem cell function with Nanopore sequencing

Project supervisor: Dr Mike Clark; Project Co-supervisor: Professor Christine Wells

Pluripotent stem cells are defined by their unique ability to self-renew and to differentiate into any cell type. Stem cells are a promising tool for the study and treatment of various diseases. As models of development, stem cells offer new ways to study cell lineage commitment and response to environmental cues. New cutting-edge gene expression technologies now allow us to look more deeply into stem cell health and behaviour by characterising the expression patterns of both genes and their splice isoforms, and particularly how this occurs in the different cell lineages that make up the early embryo. This project will utilize long-read Nanopore sequencing to decipher, for the first time, the specific isoforms that are associated with lineage commitment, and how changes in environment, such as hypoxia, alter these developmental events. This will help us to decipher the molecular makeup of stem cells, how they divide while retaining their stemness and the effects of environmental changes on stem cell function.

Project 2: Neuropsychiatric disease gene characterisation with Nanopore sequencing

Project supervisor: Dr Mike Clark

Schizophrenia and bipolar disorder are prevalent and often debilitating mental health disorders with a strong genetic component underlying disease risk. Little progress has been made in treating these disorders in recent decades, as we still don’t have a good understanding of their molecular causes. Recent studies have identified a growing number of genomic loci that associate with disease risk. However, lagging behind the identification of risk loci is the characterisation of risk genes and what about them changes in the risk condition. This project will utilize Nanopore sequencing, a ground-breaking new technique, to decipher the expression and splicing patterns of neuropsychiatric risk genes in human brain. The opportunity exists to both perform the sequencing and conduct analysis of the gene expression data. Together this will provide an unrivalled resource for understanding the expression and isoform profiles of neuropsychiatric disease risk genes, knowledge that is critical in order to translate genetic findings into a better understanding of disease pathology and identify potential treatment targets.