Fine-tuning Signalling and gene expression levels
The precise coordination of the many forces and growth factors acting upon embryonic tissues is required for the development of complex organs. We are interested in how intracellular signalling pathways are regulated during organogenesis. Many cell surface receptors use reversible tyrosine phosphorylation as a means of signal transduction. Studies in a number of biological systems have suggested that these signalling pathways are not merely ON/OFF switches but that subtle differences in signal strength and duration often result in profoundly different outcomes. Recent evidence indicate that chromatin remodelling factors fine-tunes gene expression levels during development. We are interested in understanding the various functions of the CHD7 chromatin remodelling factor in brain development.
Cerebellar morphogenesis: The cerebellum is the brain’s control centre for motor coordination and defects in cerebellar development are often associated with ataxia or medulloblastoma, the most common type of childhood cancer. We are interested in how the cerebellum is constructed during embryonic and early postnatal development. We are investigating this process using conditional gene inactivation approaches in vivo.
Supported by the Wellcome Trust
Researcher: Tian Yu
Adult stem cell function: Both regulators of intracellular signalling (e.g. Spry1) and chromatin remodelling factors are important for normal adult stem cell function. We are investigating the roles of these factors in adult stem cells in the muscle (in collaboration with Dr. Andrew Brack (Harvard) and brain.
Supported by the BBSRC
Researcher: Kieran Jones
Thymus organogenesis, pharyngeal pouch patterning and DiGeorge syndrome: Our recent experiments have indicated that several essential organs such as the thymus, parathyroid, middle ear and cranial sensory ganglia that develop wholly or in part from the pharyngeal apparatus exhibit multiple defects in Sprouty mutant mice. These same organs are affected in 22q11 deletion or DiGeorge syndrome and we are investigating the molecular and developmental basis of these defects in mouse embryos. A current interest is the function of and interaction between Tbx1 and FGF signalling in the pharyngeal endoderm during pharyngeal pouch morphogenesis
Supported by the Medical Research Council
Research team: Abigail Jackson
Chromatin remodelling and brain development
Patients affected by CHARGE syndrome suffer from a number of brain defects, including autism spectrum disorders, learning difficulties and cerebellar hypoplasia. We are using mouse models for this syndrome in which the Chd7 gene is mutated to elucidate the function of CHD7 in brain development.
Research team: Tian Yu, Katrin Danielsen, Eugenia Sanz Smachetti
Adult stem cell biology
We recently showed, in collaboration with the Brack lab at Harvard, that Sprouty1 plays an important role in adult muscle stem cells or "satellite cells". This work is continuing in collaboration with the Brack lab. In addition, we are investigating the role of Spry1 in adult neural stem cells in the adult brain.
Research team: Kieran Jones, Tian Yu