Dr David Bassett

Introduction

I have identified mutations in the zebrafish dystrophin gene as a model of muscular dystrophy, work published in Development and highlighted in Nature Reviews Genetics. My group is currently characterising the model further, and recently patented and licensed it to a drug discovery company.
I lecture on the Institute of Human Genetics' MSc in Medical Genetics.

Background

I am a developmental geneticist concentrating on modelling human diseases using the zebrafish. I have worked on the development of both the early CNS and skeletal muscle. Currently I am concentrating on further development of zebrafish dystrophin mutants as a model of Duchenne Muscular Dystrophy.
I am also involved in presenting the etrhics and science of stem cell technology to the general public in collaboration with the International Centre for Life and NESCI.

Roles and Responsibilities

As a member of the Academic Staff and a Senior Research Associate, I am responsible for the funding and research of my own group within the IHG. This includes the use and care of our own zebrafish models. I am also one of only three members of staff charged with the administration of the Institute's growing computer networks.

Qualifications

I have a BSc (with First Class Honours) in Zoology from University College London.
I have a PhD from the University of London (King's College and UCL) in the Early Development of the Central Nervous System. My supervisor was Profesor Stephen Wilson.

Previous Positions

I was a Research Associate at the Department of Anatomy and Developmental Genetics at University College London.
I was also a Research Associate at the Medical Research Council's Human Genetics Unit in Edinburgh.

Memberships

British Society for Developmental Biology

Honours and Awards

I received the Muscular Dystrophy Campaign's Peter Walker Fellowship Award for the most promising work carried out under any of their Project Grants.

Languages

English French German

Informal Interests

I do try to make some time to get out and about in the countryside and up into the mountains of Scotland. The fresh air provides a chance to get back to the "bigger picture" with regards to my work.

Research Interests

We are concentrating on modelling a group of inherited diseases that cause gradual loss of function in human cardiac and skeletal muscle, in addition to congenital defects of these tissues. Muscular dystrophies and cardiomyopathies are often caused by defects in the Dystrophin-Associated Protein Complex (DAPC), which is thought to maintain the integrity of cell membranes during muscle contraction. We have established a zebrafish model of dystrophin deficiency which manifests as Duchenne and Becker muscular dystrophies (DMD/BMD) and X-linked dilated cardiomyopathy (XLCM). This zebrafish model has already revealed a novel pathological mechanism of skeletal muscle degeneration, a failure of muscle fibre end attachments similar to mammalian myomuscular junctions. This model will be used to further investigate the pathological processes responsible for skeletal muscle degeneration.

Other Expertise

I have a keen interest in developmental genetics as a whole, and particularly in the induction and specification of cell fates by signaling events, morphogenesis and transcriptional control. I also follow the fields of muscular dystrophy and cardiomyopathy research with a view to understanding the processes occurring in these genetic diseases.

Current Work

We are currently examining the effects of glucocorticoids on skeletal muscle pathology in order to validate assays for the effects of novel drugs. Prednisone and prednisolone are the only drugs currently available for the treatment of Duchenne and Becker Muscular Dystrophies, and we will try to gain insights into their mechanisms of action along the way.

Future Research

We hope to devise assays for using dystrophic zebrafish for drug screening.

Esteem Indicators

My paper in Development in 2003 on the cloning and phenotype of a zebrafish model of Duchenne Muscular Dystrophy was reviewed in Nature Genetics Reviews as a Highlight (Nature Reviews Genetics 5, 4 (2004); doi:10.1038/nrg1263).
I received the Muscular Dystrophy Campaign's Peter Walker Fellowship Award for the most promising work carried out under any of their Project Grants.
I am collaborating on the characterisation of dystrophin deficient cardiomyopathy with Professor Calum MacRae in Boston, who is preeminent in the field of zebrafish heart research.
I am collaborating on functional studoes of the Fukutin-Related Protein (FKRP) and Large genes with Professor Volker Straub in the Institute and Professor Jane Hewitt in Nottingham. These proteins modify dystrolycan and are limb girdle muscular dystrophy loci in humans.
I am collborating with Professor Judith Goodship on the characterisation of a candidate gene for cardiac asymmetry defects.

Funding

The zebrafish facility has been awarded £80,000 from a North-East charity, the Sir James Knott Trust, in funding for a zebrafish facility. I have received £85,000 from Heart Research UK to study the heart pathology in dystrophin deficient zebrafish and £21000 from the Newcastle University Hospitals Trust Special Trustees. I also received a prize of £5,000 from the Muscular Dystrophy Campaign for the most promising research project funded by them.

Industrial Relevance

The development of zebrafish embryonic models of genetic disease is intended to lead to high throughput drug screening in collaboration with the pharmaceutical industry. Indeed, I am acting as consultant to a UK-based pharmacuetial company on the use of dystrophic zebrafish in drug testing which has licensed from us their use in drug screening.

Patents

I hold a patent jointly with my former supervisor Professor Peter Currie and the Victor Chang Cardiac Research Institute in Sydney. The patant covers the use of the dystrophin mutant zebrafish as a model of Duchenne Muscular Dystrophy and dilated cardiomyopathy and has been licensed to a UK-based pharmaceutical testing company for drug screening.

Keywords

zebrafish, dystrophin, DMD, Duchenne Muscular Dystrophy, cardiomyopathy, genetics, sapje, embryos, teaching

Undergraduate Teaching

I am undertaking the Introduction to Teaching and Learning in Higher Education Course, and willing and able to teach genetics, developmental biology.

Postgraduate Teaching

I lecture on the Institute of Human Genetics' MSc course in Human Medical Genetics, on Module CMS804. I teach on genetic model organisms with relevance to development, disease and drug discovery.