Cellular genetics, cell biology, gene trap mutagenesis, pharmacogenomics

Gene mutation identification in patients has defined and explained human heritable disease. Mouse transgenic technologies have enabled the creation of in vivo models for these human disease. In contrast to these profound genetic advances, the use and study of mutations in individual human cells is somewhat neglected - and yet individual cells are the site of primary action for many disease mutations and pharmacogenetic interactions.

We are employing gene trap mutagenesis in cultured cells as a means to create libraries of human cells, each with a single damaging gene mutation. These libraries of cells can be screened for altered biological or pharmacological properties. For example, in the Institute we have used this approach to screen for mutant genes which affect the way that their cells respond to the mood stabiliser drug lithium, treatment with chemotherapy drugs, survival in a cellular model of Alzheimer's disease, and infection by pathological bacteria. In each case we have identified genes that tell us about the underlying biology, the causes of differing drug responses/side-effects, and the potential targets for new medicines. This approach is powerful, adaptable, rapid and can objectively guide researchers along novel avenues of study.

We are looking for enthusiastic PhD students who wish to train in this exciting area. Being adaptable, means that we can offer a wide range of specific project areas that use the approach - from pharmacogenetics to basic biology. Ben Pickard has almost 25 years of research experience and has supervised a number of successful PhD projects in which students have been personally trained in all aspects of the field. He has acted as internal and external PhD viva examiner on numerous occasions, and this experience will ensure that the student produces the best possible thesis within the study timeframe. 

Tissue culture, cell biology, immunofluorescence, molecular biology and molecular genetics techniques including PCR, cloning, sequencing, next generation sequencing, and CRISPR.

A gene trap mutagenesis screen for genes underlying cellular response to the mood stabiliser lithium

Gow, M., Mirembe, D., Longwe, Z. & Pickard, B. S. May 2013 In : Journal of Cellular and Molecular Medicine. 17, 5, p. 657-663 7