Centre for Synthetic Biology and the Bioeconomy

Staff Profile

Professor Jane Endicott

Prof of Cancer Structural Biology

Background

Current position

Professor of Cancer Structural Biology

Roles and responsibilities

NICR Executive Board
NICR Strategy Board
FMS Research Career Development Group


Area of expertise


Cell cycle structural biology              

Phosphorylation transcription

Since October 2011, I have been Professor of Cancer Structural Biology in the Northern Institute for Cancer Research, Newcastle University.  My group is pursuing structure-function studies of protein complexes involved in regulating transcription and progression through the eukaryotic cell cycle.  We are also providing structural biology support to projects within the NICR Drug Discovery Group.

I studied Biochemistry at Corpus Christi College, the University of Oxford and then moved to the laboratory of Victor Ling at the Ontario Cancer Institute, Toronto to complete my PhD. I returned to Oxford in 1991 as a Junior Research Fellow of the National Cancer Institute of Canada to join the laboratories of Professor Paul Nurse and Professor Louise Johnson to pursue structural studies of cyclin-dependent protein kinases (CDKs) and their regulators.  I was awarded a Royal Society University Research Fellowship in 1995 and appointed to a University Lecturership in the Laboratory of Molecular Biophysics, University of Oxford in 1998. During my time at Oxford I held a College Fellowship at St. Cross College, where I am now an Emeritus Fellow and a Lecturership at Trinity College. 

Funding and collaborations

2018-2020       MRC DPFS Award.  With C. Cano, M. Martin, M, Noble and S. Wedge 

2016-2021       MRC Programme Grant.  With M.E.M. Noble “CDK-containing macromolecular assemblies”

2015-2020       CRUK Programme Grant. Lead PIs  S. Wedge and M. Waring, co-PIs C. Cano, J.A. Endicott, I. Hardcastle, D.R. Newell, M.E.M. Noble “The Cancer Research UK Programme for Drug Discovery at the Northern Institute for Cancer Research, Newcastle University”

2015-2020       CRUK Centres Network Accelerator Award. “Accelerating drug discovery through a networked structural biology resource”.

2012-2020       Astex Strategic Drug Discovery Alliance (Astex Pharmaceuticals, Newcastle University and CRT) Lead PIs (Newcastle): C. Cano, J.A. Endicott, I.R. Hardcastle, I. Hickson, M.E.M. Noble, M. Waring and S. Wedge

External research roles and memberships

2018-present  CRUK Science Committee

2016-present  MRC Non-Clinical Training and Career Development Pane, Deputy Chair

2012-present  Fellow, Royal Society of Biology

2003-present  Faculty of 1000

Honours and awards

2014    MRC Suffrage Science Award

Google scholar: Click here.

Research

Research interests

Structural and functional characterisation of the cyclin-dependent protein kinase (CDK) family
Development of small molecule CDK inhibitors
Biophysical assays and structure determination for anti-cancer drug design

Current work

The growth and division of cells is strictly controlled at the molecular level by a number of enzymes that include the cyclin dependent protein kinases (CDKs). CDKs 1, 2, 4 and 6 are switched on and off in an orderly sequence, to ensure that cell division starts and stops at the required time. Other members of the CDK family (for example CDKs 7, 8 and 9) are also important for the control of transcription, the process by which genes are transcribed into messenger RNA that in turn serves as the template for protein synthesis. Regulation of transcription ensures the timely expression of proteins required for cell growth and differentiation. Errors in either the control of cell cycle progression or transcription can lead to uncontrolled cell growth and proliferation.

Although CDK family members are closely related in sequence, biological studies have revealed that each has unique properties. Our work, primarily using the technique of X-ray crystallography, allows us to see the structures of CDKs and the complexes they form at atomic resolution and to learn how they differ from each other. To this end we characterise and reconstitute selected CDK-containing complexes using heterologous expression systems and then study them by structural, biochemical, biophysical and cell-based methods. Aberrant CDK activity has been linked to cancer, neurological diseases, and rheumatoid arthritis. CDK-selective inhibitors in clinical trials for the treatment of cancer act by binding to the CDK active site to block CDK activity. Compounds that block other interactions made by CDK-cyclin complexes represent an alternative target for CDK-directed therapies. Our work aims to identify CDK-cyclin protein interaction sites to further understand the regulation of this important enzyme class and to aid the further development of CDK inhibitors. 

For further details about our work, please visit the Cell Cycle Structural Biology and Structural Biology sections of Cancer Drug Discovery Research at the NICR. 

Selected Publications

Wood, D.J., Korolchuk, S. Tatum N.J., Wang, L.-Z. Endicott, J.A. Noble, M.E.M., Martin, M.P. (2019) Differences in the conformational energy landscape of CDK1 and CDK2 suggest a mechanism for achieving selective CDK inhibition. Cell Chem. Biol. 26:121-130.

Wood DJ, Endicott JA. (2018) Structural insights into the functional diversity of the CDK-cyclin family. Open Biol. 8(9). pii: 180112. doi: 10.1098/rsob.180112. 

Hallett, S.T., Pastok, M.W., Morgan, R.M.L., Wittner, A., Blundell, K.L.I.M., Felletar, I., Wedge, S.R., Prodromou, C., Noble, M.E.M., Pearl, L.H. and Endicott, J.A. (2017) Differential regulation of G1 CDK complexes by the Hsp90-Cdc37 chaperone system. Cell Repts, 21, 1-13.

Brown, N.R., Korolchuk, S., Martin, M., Moukhametzianov, R., Stanley, W. Noble, M.E.M. and Endicott, J.A. (2015) CDK1 structures reveal conserved and unique features of the essential cell cycle CDK. Nature Comms, 6: 6769.

Takaki, T., Echalier, A., Brown, N.R., Hunt, T., Endicott, J.A., and Noble, M.E.M., (2009) The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc Nat Acad Sci USA 106, 4171-4176. 

Theme web pages

Cell Cycle Structural Biology
Cancer Drug Discovery

 

Teaching

Teaching and supervision

PhD and MRes student supervision

I look forward to welcoming Masters and undergraduate project students with an interest in

            Cell cycle regulation

            CDK structural biology

Undergraduate course BGM2002, Cell cycle CDKs: Structure and Function

Undergraduate course BGM2060, Proteins and Enzymes

External examining and teaching

BCA/CCP4 Protein Crystallography Summer School, lectures covering protein expression, purification and crystallisation


Publications