Prestigious Collaborative Award and Seed Award funding from the Wellcome Trust has been awarded to researchers at Great Ormond Street Hospital (GOSH) and the UCL Great Ormond Street Institute of Child Health (ICH). The awards will support pioneering laboratory-based research which will help shed light on the underlying genetic and molecular causes of rare childhood conditions.
Professor Phil Beales and Dr Dagan Jenkins have been awarded a £3.2 million Wellcome Trust Collaborative Award in Science, and will jointly lead on a large-scale project that brings together nine basic scientists located at five research institutions across London and Germany.
The project will use a highly innovative approach which combines gene-editing, protein network analysis and computational biology to systematically characterise a particular category of missense mutations that cause skeletal ‘ciliopathies’ – a group of diseases where the small hair-like structures on the outside of cells (the cilia) are defective. These mutations cause a variety of disorders, in particular skull fusion at birth (craniosynostosis) and a small rib cage. This project will help to unravel the complex mechanisms underlying genetic disease and shed insight into the fundamental properties of protein interaction networks. Once developed, this approach could be applied to up to 1,000 other conditions caused by the same category of mutation.
In addition, Dr Conor McCann and Dr Helena Kilpinen have both secured Seed Award funding from the Wellcome Trust. The awards will allow Drs McCann and Kilpinen, who are both Research Associates at ICH and GOSH, to develop research ideas that will later form part of larger grant applications.
Dr McCann’s project will investigate the underlying causes of serious gastrointestinal conditions such as achalasia, gastropareis and diabetes. The study will explore how damage to nerves in the gut can affect the muscle cells that are responsible for moving of food along the digestive tract. A better understanding of the molecules and cells involved in this process will help researchers move closer to treatments for children with these life-limiting conditions.
Dr Kilpinen’s project will compare two different types of stem cells – those obtained from patients with rare genetic conditions (patient-derived induced pluripotent stem cells; iPSCs) and those that are derived from healthy individuals but have been modified to carry the mutation that causes the rare condition. The study will explore the relative pros and cons of using these two types of cells to model rare conditions in the laboratory and help design more accurate studies to understand their cause.
These awards build on previous work supported by National Institute for Health Research (NIHR; all), Guts UK (Dr McCann), Medical Research Council (MRC eMedLab; Dr Kilpinen) and a MRC New Investigator Research Grant (Dr Jenkins).