Dr Benjamin Housden
Research Fellow (LSI)
01392 72 7475
Living Systems Institute T04.13
Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD
My research is focussed on using interdisciplinary methods to study how genetic mutations lead to disease. This involves a combination of new technology development and high-throughput genetic screening to analyse gene functions and to identify and characterise candidate drugs to treat diseases. The development of new methods to identify effective drugs is vitally important because current methods suffer from a high failure rate that slows the development of new therapies.
- Ph.D., University of Cambridge, 2010
- M.A., University of Cambridge, 2005
Dr. Housden began his research career in the laboratory of Professor Sarah Bray at the University of Cambridge. There, he studied the direct transcriptional outputs of Notch signaling and crosstalk with the EGFR pathway using Drosophila as a model system. For his postdoctoral work, he joined Professor Norbert Perrimon’s laboratory at Harvard Medical School. Here, his interest in gene networks led him to develop new genetic screening methods to identify genes that could be targeted to treat human diseases. Since joining the Living Systems Institute in 2017, Dr. Housden’s laboratory has focused on developing new methods to enhance their ability to identify new therapeutic targets for disease and applying these methods for drug discovery.
- Research Fellow - University of Exeter; 04/2017 to present
- Postdoctoral Fellow - Harvard Medical School; 09/2011 to 03/2017
- Postdoctoral Fellow - University of Cambridge; 12/2010 to 08/2011
- Katarzyna Sierzputowska (PhD student with Wakefield lab)
- Jeong Yeol Lee (PhD student with Bhinge lab)
- Amy Housden (Research technician)
- Emma Hottinger (Research technician)
- Chris Baxter (Masters student with Oltean lab)
- Ben Jenkins (PhD student with Richards lab)
- Sonali Sengupta (Postdoctoral research fellow)
Research in our group is focused on developing new methods and technologies to allow more sensitive and higher throughput genetic screens to be performed. This includes optimisation of screening methods via the application of liquid handling automation, development of new molecular biology techniques to enhance the performance of genetic tools and the application of machine learning to better analyse screen data. Together, these advances will allow us to perform larger and more reliable screens, which can be applied to both fundamental biological investigations and drug-discovery.
In addition, we have several ongoing projects to apply the new screening methods that we develop to identify new drug-targets for human diseases. We are currently working on Tuberous Sclerosis Complex, Neurofibromatosis type 1, Amyotrophic Lateral Sclerosis and several mutations linked to sporadic cancers.
Project 1: Accelerating drug discovery by developing improved technologies for synthetic lethal screens
The overall aim of this project is to improve the process of identifying new drug targets for the treatment of human diseases. We are using an interdisciplinary approach to improve all aspects of the high-throughput screens that are often used for drug target discovery. For example, we developed a new assay for cell viability called Variable Dose Analysis (VDA), which improves the sensitivity of screens and enables better detection of candidate targets amongst essential genes. In addition, we are working with industry partners to develop miniaturised and automated methods for VDA screening. Finally, we are developing machine-learning methods to improve the analysis of screen data. Together, these improvements will facilitate rapid identification of the most promising candidate drug targets for further development.
Project 2: Identification and characterisation of novel drug targets for Tuberous Sclerosis Complex (TSC)
Tuberous Sclerosis Complex (TSC) is a tumourigenic disease caused by mutations in the TSC1 or TSC2 genes and is currently treated with rapamycin. However, this drug is insufficient because it prevents tumour growth but does not kill tumour cells. Therefore, tumours regrow rapidly when treatment is stopped. The aim of this project is to use the VDA screening method to identify single drugs and combinations of drugs that specifically kill TSC mutant cells. Such drugs represent promising new candidates for the treatment of TSC. We are also using similar methods to identify candidate drugs to treat other diseases including Neurofibromatosis type 1, Amyotrophic lateral sclerosis (ALS) and sporadic cancers.
Project 3: An integrated analysis of the protein-protein interaction network of the conserved mitotic kinase, Polo
Katarzyna Seirzputowska (Kasia) is a PhD student in the lab, co-supervised with James Wakefield, who is studying the roles of the kinase Polo during cell division. Kasia is applying the VDA screening method to search for genetic interactions with Polo and will then further characterise these interactors to gain a deeper understanding of both the regulation and downstream mechanisms of Polo function.
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Benjamin_Housden Details from cache as at 2022-07-07 05:04:53