Overview

My research interest has always been that of mitosis and cell division, stimulated by the fundamental beauty of the process as viewed using a fluorescence microscope, and its key role in diseases such as cancer. Cell division is orchestrated by two main microtubule (MT) based structures called the ‘spindle apparatus’ and the ‘central spindle’, which function at different times to co-ordinate this dynamic process. We want to understand how these systems organise themselves, and what governs the similarities and differences between them in diverse types of cell, at different stages of development, and during disease. In order to learn as much as possible, we take a multi-disciplinary approach, combining proteomics, bioinformatics and quantitative image analysis with qualitative, descriptive cell and developmental biology, and genetics. I am a member of the Cell Biology research group.

Qualifications

1999 PhD Wellcome/CRUK Institute for Cancer Research and Developmental Biology, University of Cambridge, UK
1995 BSc (Hons) in Biochemistry, University of Bristol

Career

2018-current Professor of Integrative Cellular Biology and Head of Department of Biosciences, University of Exeter

2013-2018 Associate Professor if Integrative Cellular Biology, University of Exeter

2010-2013 Senior Lecturer in Cell Biology, School of Biosciences, University of Exeter
2007-2009 Director, Life Sciences Interface Doctoral Training Centre, University of Oxford
2004-2007 Lecturer in Biology (Deputy Director) Life Sciences Interface Doctoral Training Centre, University of Oxford
2003–2004 Departmental Lecturer in Biology / Co-ordinator, MSc in Integrative Biosciences, University of Oxford
2000-2002 MRC Postdoctoral Research Associate, University of Bristol
1999-2000 EU TMR Postdoctoral Research Associate, Dipartmento di Genetica e Biologie Molecolare, University of Rome, Italy

Links

• The Wakefield Lab website

Research group links

• Cellular and Chemical Biology

Back to top

Research

Research interests

Background (General)
Every living thing renews itself by a process of cell division. In order to produce two new identical cells from one existing cell, the genetic material, the chromosomes, must first be replicated and the volume of the cell must increase. During the process defined as cell division itself, these duplicated chromosomes align in the centre of the cell before one copy of each chromosome is moved to opposite sides of the cell. Finally, the cell physically cleaves in two, usually at the centre of the cell, producing two daughter cells, each identical to themselves and to the original cell.

All cells use protein fibres termed microtubules (MTs) order to faithfully divide. These fibres are made up of repeating units of a protein called tubulin that can be added or taken away from the ends of existing MTs, allowing them to grow and shrink. Other proteins in the cell, called MT associated proteins (MAPs) are able to alter the properties of the MTs, causing them to grow or shrink more quickly, to link existing MTs to each other, or to link the ends of the MTs to chromosomes or other structures in the cell. In this way, MTs can be organised into dynamic structures, capable of doing different things. During cell division, two main MT structures are important - the spindle apparatus, which makes sure the chromosomes line up and are moved apart correctly, and the central spindle, that allows the cell to cleave precisely in two.

Background (Technical)
Cell division is orchestrated by a microtubule (MT) based structure called the spindle apparatus. In most animal cells, the formation of the spindle apparatus is mediated by complex interactions between MTs nucleated by the centrosome, those organised by mitotic DNA, and those seeded by the growing spindle itself. These populations of MTs are organised by a multitude of MT associated proteins (MAPs), including protein motor complexes, to form a polarized and focused spindle capable of chromosome segregation. Following movement of sister chromatids to the spindle poles in anaphase, a bundle of MTs form between the separating DNA. This central spindle assists in the formation of the contractile ring, a transient actin and myosin-II based structure, which is then able to direct cytokinesis.

Aim of the lab
We want to understand how the spindle apparatus and central spindle are organised, and what governs the similarities and differences between these structures in different types of cell. In order to learn as much as possible about this process, we use a combination of quantitative analytical methods and qualitative, descriptive biology.

Why fruit flies?
Drosophila melanogaster has proved to be an excellent system both for studying cell division, and for the isolation of proteins that function during mitosis. There are a number of other labs throughout the world working on distinct aspects of cell division in this model organism. It is a close-knit community of scholars who are open and enthusiastic about advancing the field as quickly as possible. 

Other research interests
Obviously, I look to oversee the research being undertaken in the lab in general. In addition, I am interested in the relationship between different scientific approaches, and the way in which they can be combined to provide advances in our understanding of biological processes. The move towards quantitative techniques, driven by technological advances in physical science methods, coupled to the wealth of information accumulated within biology using high-throughput approaches, is now allowing us to measure and analyse sub-cellular processes with a degree of accuracy not previously possible. This provides the researcher with “real” data, which can be combined with statistical methods and powerful computational tools to build models of biological processes that can be tested. However, I believe it is important to view such analyses within the context of the biological process being studied. Humans are able to process visual information and relate it to their previous experiences and accumulated knowledge in a manner impossible for computers. Immersing oneself in the viewing experience can lead to a greater understanding of the way in which a biological process 'works'. Such experiential, intuitive biology has been practiced for centuries and has led to many of the great advances in biology, medicine and related disciplines. We currently have a research grant, funded by the Arts and Humanities Research Council (AHRC), in collaboration with a Philosopher of Biology, Prof John Dupre, and artist Gemma Anderson, exploring the value of drawing in the hypothesis-forming process. By combining the recently advanced quantitative techniques and historically valuable qualitative approaches, I believe science will be able to move towards its goal of understanding the world in which we live more quickly than using one approach alone.

Research projects

1. Identification and characterisation of novel MAPs with roles in cell divis
2. Understanding the way in which the Augmin complex works to supplement microtubule nucleation from within the mitotic spindle
3. Understanding the role of the chromosomal passenger complex (CPC) in central spindle assembly and cytokine
4. Automated quantitative analysis of microtubule and chromosome dynamics

Research networks

Hiro Ohkura, University of Edinburgh, UK
David Sharp, Einstein College of Medicine, NY, USA
Maria Grazia Giansanti, Universita di Roma 'La Sapienza', Italy
Charlotte Deane, Department of Statistics, University of Oxford, UK
Alison Noble, Department of Engineering, University of Oxford, UK

Back to top

Publications

Back to top

External Engagement and Impact

Awards/Honorary fellowships

MRC ROPA (Realising Our Potential Award) Jan 2001- April 2002

EU TMR Award, 1999-2000

Wellcome Trust Prize Studentship, 1995-1999

Nuffield Foundation Summer Scholarship, 1994

Committee/panel activities

Exeter

Chair of Streatham Biosciences Education Team  (Aug 2010 - July 2012)
Member of Biosciences Strategy Group  (Aug 2010 - July 2012)
Member of CLES Education Strategy Group (Aug 2010 - July 2012)
Member of CLES Management Group (Aug 2010 - July 2012)
Member of EPSRC CDT working group (Jan 2013 - current)
Member of Living Systems Building working group (Sept 2012 - current)

Outside Exeter

Membership Secretary, British Society for Cell Biology (2013 - present)
Chair of LSI DTC Directorate, University of Oxford (Oct 2007 - Dec 2009)
Member of DTC Advisory Board, University of Oxford (Oct 2004 - Dec 2009)
Member of Divisional Education Committee, University of Oxford (Oct 2007 - Dec 2009)

Editorial responsibilities

Invited Guest Editor, Chromosome Research, July-Dec 2010

Invited lectures

1.EMBO Drosophila Cell Division Cycle Meeting, Sept 2013. Invited talk
2. Gurdon Institute, Cambridge, May 2013. Invited talk
3.UK Drosophila Cell Developmental Biology Workshop, May 2013. Invited talk
4. Birkbeck College, London, April 2013. Invited talk
5.University of Cardiff, December 2012. Invited talk
6. University of Bath, December 2012. Invited talk
7.University of Reading, November 2012. Invited talk
8.Vice Chancellor's Conference, Anglia Ruskin University, September 2012.    Invited talk
9. ASCB Annual Meeting, San Diego, USA, December 2009. Invited talk
10. UK Council for Graduate Education, Manchester, June 2009. Invited talk
11. University of Cambridge, September 2007. Invited talk
12. University of Rome, Italy, June 2008. Invited talk
13. EMBO Chromosome Segregation and Aneuploidy Meeting, Finland, June    2007. Invited talk
14. University of Edinburgh, September 2006. Invited talk
15. EMBO Drosophila Cell Cycle Meeting, Porto, Portugal, June 2006. Invited talk
16. University of Bristol, May 2006. Invited talk
17. EMBO Drosophila Cell Cycle Meeting, Siena, Italy, June 2001. Invited talk

Research funding

External:

Principal Applicant, 3 year Project Grant, BBSRC (2013-2016) – “Microtubule Associated Proteins with roles in mitosis: A systems approach”. Total funding – £472,000 FEC

Principal Applicant, 3 year Project Grant, Cancer Research UK (2010-2013) – “The role of the Chromosomal Passenger Complex in central spindle formation and cytokinesis” Total funding £455,000 FEC equivalent

Principal Applicant, 3 year Project Grant, The Wellcome Trust (2004-2007) – “Cellular and molecular analysis of ciottoli, a male meiotic mutant in Drosophila". Total funding £462,000 FEC equivalent

Principal Applicant, 3 year Project Grant, BBSRC (2003-2006) - "Identification of mitotic phospho-proteins in Drosophila". Total funding £535,000 FEC

Principal Applicant, Royal Society (2003-2004) - "Identification of mitotic phospho-proteins in Drosophila". Total funding £14,500 FEC equivalent

Internal (since 2010):

Principal Applicant, University of Exeter ISSF Wellcome Trust Seed Corn Fund (2012/13) – “Generation of affinity purified, fluorescently labelled antibodies to disrupt cell division”. Total funding – £13,444 (non-FEC)

Principal Applicant, University of Exeter CLES Strategic Development Fund (2011/12) – “Using quantitative proteomics to understand cell division”. Total funding – £19,250 (non-FEC)

Principal Applicant, University of Exeter Bridging the Gap Pilot Grant (2011/12) – “Symmetry breaking during cell division”. With Peter Ashwin (Mathematics, Exeter). Total funding – £1,760 (non-FEC)

Other:

Principal Applicant, EMBO Workshop Fund (2013) - "University of Exeter / EMBO Drosophila Cell Division Cycle Meeting". Total funding - £36,500

Workshops/Conferences organised

The Dynamic Cell (BSCB Autumn Meeting). For Sept 2014

EMBO Drosophila Cell Division Cycle Meeting. For Sept 2013.

Forum for Scientific Method in Biology, University of Oxford, March 2009.

Back to top

Teaching

Modules

2023/24

Information not currently available

Back to top

Supervision / Group

Postdoctoral researchers

Back to top