Professor Ken Siddle
Professor of Molecular Endocrinology
 |
I have worked in the Department of Clinical Biochemistry since 1978,
and have been Professor of Molecular Endocrinology since 1990. I am
also a Fellow of Churchill
College. I have an active research group studying various aspects
of the structure and function of receptors for insulin and insulin-like
growth factors. I lecture on insulin action and diabetes to both medical
and science undergraduates, and am also involved in training programmes
for postgraduates. When I am not at work I enjoy mountaineering,
playing and watching cricket (I help to run the Cambridge
University Cricket Club), gardening and bird-watching. |
Contact: Tel: 01223 336789 (office), 01223 336793 (lab)
Email: ks14@mole.bio.cam.ac.uk
Research Interests
Our research aims to achieve a better understanding, at the molecular level, of the mechanism of insulin action, the basis of specificity in the effects of insulin and insulin-like growth factors, and
the causes of insulin resistance and non-insulin dependent diabetes. Our interests extend from ligand-receptor interactions, through the biochemistry and cell biology of signalling pathways, to biological
responses with particular emphasis on adipose tissue.
For a list of my principal publications click here
My laboratory interacts closely
with those of my colleagues Steve
O'Rahilly, Jazz
Sethi and Paul
Luzio, with whom I have a number of joint projects. We have links
with many centres in the UK, Europe, America and Australia, for exchange
of reagents and ideas. We work mostly on cultured cell lines, and occasionally
on animal or human tissues. We have always made heavy use of antibodies,
both polyclonal and monoclonal, and still like to produce our own reagents
wherever possible. We therefore have particular expertise in this area,
including use of peptides or fusion proteins as immunogens, purification
and assessment of antibodies, and applications in immunoprecipitation,
immunoblotting and immunoassay. We have adopted a broad range of analytical
and molecular biological techniques, including both proteomic and microarray
approaches to expression profiling. We also have substantial experience
in a variety of metabolic assays (glucose uptake, glycogen synthesis,
lipolysis) and signalling pathways and in subcellular fractionation and
protein purification. The Department is well equipped for all these techniques,
and provides a challenging research environment in a clinical setting
and in close proximity to many laboratories of international standing.
Current projects include
Receptor structure and ligand binding
- Structural requirements for high affinity ligand binding, by expression
of soluble receptor fragments and receptor chimeras
- Crystallisation of ligand receptor complexes for detailed structural
analysis
Receptor expression and specificity
- Profiling insulin and IGF action on gene transcription and mRNA translation
using microarrays and proteomics
- Mechanisms regulating expression of insulin and IGF receptors, including
control of translation and degradation
- Function of insulin/IGF hybrid receptors, including regulation of
assembly and signalling potential
Intracellular signalling pathways
- Comparison of signalling by insulin and IGF receptors using chimeric
receptor constructs expressed in adipose and muscle cell lines
- Role of adaptor proteins of the Grb10/Grb14 and APS/SH2-B families,
which interact directly with insulin and IGF receptors
- Role of Sprouty proteins and Sulfiredoxin in modulating intracellular
signalling and insulin sensitivity
Funding
Wellcome Trust
BBSRC
Diabetes UK
Diabetes Research and Wellness Foundation
Group members
| Professor Kenneth Siddle |
Professor of Molecular Endocrinology and group leader |
| Dr Dirk Hadaschik |
Postdoctoral Research Associate |
| Dr Simon Ridley |
Postdoctoral Research Associate |
| Mr Keith Boyle |
Research Assistant and PhD student |
| Mr Jonathan Bray |
PhD student |
| Ms Samira Benyoucef |
PhD student |
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