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.

J.G.Wakefield@exeter.ac.uk

The chromosomal passenger complex (CPC) is a key regulator of cell division and has crucial roles throughout the cell cycle. This complex consists of the Aurora B kinase and three other subunits – Incenp, Borealin and Survivin – which are essential for its highly dynamic localisation (see movie) and activity. The CPC regulates various stages of cell division – spindle assembly, chromosome alignment, correction of microtubule-kinetochore attachment errors, central spindle and ultimately cytokinesis.

The mechanisms by which it regulates central spindle formation and cytokinesis are particularly poorly understood. Some proteins involved in these processes are known to be substrates of the CPC – myosin light chain, EVI5, centralspindlin – but how the CPC regulates these processes is still unclear.

I am using proteomic approaches to attempt to identify novel Aurora B substrates and interactors of the complex. I am using proteomic and cell biological approaches to understand how the change in behaviour of the CPC between metaphase and anaphase is controlled. Using genetic and cell biological approaches I aim to determine how the action of the CPC relates to known processes involved in cytokinesis. For these genetic experiments, we are taking advantage of the male meiosis specific Borealin homolog, Australin, previously identified by our lab, allowing us to disable CPC function specifically in the meiotic divisions. These investigations will increase our understanding of the CPC’s role in regulating central spindle formation cytokinesis.

Prior to joining the wakefield lab, I did my PhD on the role of The N-end rule pathway of proteolysis in regulating hormonal control of seed germination and dormancy in Arabidopsis (see Holman et al. 2009) with Prof. Mike Holdsworth at the University of Nottingham.

When I'm not in the lab, I enjoy brewing and drinking beer, rock climbing, tractor spotting with my young son and the freedom of not having to prevent my lab mates from injuring themselves or others.

P.D.Jones@exeter.ac.uk

Protein-protein interaction (PPI) networks are becoming increasingly popular guides to help biologists identify and target uncharacterised proteins that might possess a putative function in different biological processes.

In my inter-disciplinary project, we created an extended PPI network, or interactome, for mitotic microtubule-associated proteins (MAPs) in Drosophila. Each protein, or node, in this network was annotated with different experimental and bioinformatics data, and then using a statistical model, we scored each protein based on the predicted likelihood of their involvement in mitosis. By combining and using multiple types of available biological data, our interactome not only predicts the likelihood of a mitotic role for our putative MAPs but also unravels the inter-relationship of different proteins and their functions.  This gives us an integrated view of the process and guides our in vivo study of novel mitotic proteins. I am now chasing some very interesting candidate proteins (back in the wetlab) using an array of methods from biochemistry, cell biology and genetics.

I come with a background in biology – a BSc in Biotechnology from the University of Peshawar (Pakistan) and an MSc in Integrative Bioscience from the University of Oxford (UK). I am now an HEC scholar pursuing a DPhil at Oxford as part of the Oxford Protein Informatics Group.

Outside the lab I’m working on my biotech startup, busy on Skype with my family back home or searching for someone to play squash with. I also read alot – my non-biology interests start from Education Policy and Entrepreneurship to Foreign Policy, all the way to History and Theology.

The mitotic spindle is the structure responsible for aligning and separating chromosomes during cell division. Failure to successfully build a mitotic spindle can hinder this process, leading to cell death and genetic defects that could give rise to cancers or developmental disorders.

The key components of the mitotic spindle are microtubules. There are multiple mechanisms involved in the polymerisation and structuring of microtubules. These include the two centrosomes on the nuclear periphery at mitosis, key microtubule organising centres in metazoans responsible for nucleating and anchoring microtubules. Kinetochores, complex structures located on chromosomes, are responsible for “capturing” and stabilising microtubules during mitosis, as well as nucleating their own microtubules. Additionally, a Ran-GTP gradient exists around chromosomes during early mitosis, helping promote microtubule growth in their direction. Augmin is another microtubule nucleator, acting to amplify the number of microtubules. There are also numerous other mechanisms in a variety organisms that play a role in mitotic spindle formation. 

The relative roles of these pathways and the proteins behind them are not fully understood. Moreover, it is possible that as of yet unknown processes also play a role in mitotic spindle assembly. 

My research focuses on the multiple apparatus that contribute to the building of the mitotic spindle, and the pathways and molecules that underpin these mechanisms. My model system is the single celled, multi-nuclei Drosophila early syncytial embryo. This enables me to use high resolution confocal microscopy to obtain 4-dimensional images of mitotic spindles forming in vivo. This system also allows the use of biochemistry, proteomics, genetics and interfering antibody injection. 

Before starting my PhD in 2010 I graduated from the University of Exeter with a first class BSc in Biosciences. My third year research project was on molecular variability of the emerging human pathogen P. boydii with Dr Chris Thornton. 

Additional to my lab work, I enjoy finding new and ever more innovative ways to annoy jack, creating masks of former lab members and sticking them up in various locations around Exeter and being embarrassingly drunk at almost any bioscience event that involves alcohol!

dh252@exeter.ac.uk

There are three major areas of microtubule nucleation in eukaryotic cells.  They are the centrosomes, chromosomes, and pre-existing microtubules.  The Augmin complex, consisting of 8 different proteins, is responsible for regulating microtubule generation around pre-existing microtubules.  The current predominant model is that Augmin recruits γ-Tubulin Ring Complex to the microtubules which then nucleates new microtubules.

Using an in vitro approach, I am purifying GFP-tagged Augmin, to see if and where it binds to microtubules.  I am also seeing if Augmin can nucleate new microtubules.  Using an add-back approach, I will determine if human Augmin and drosophila Augmin are functionally conserved.  Using an in vivo approach I will examine the role of Augmin in various drosophila tissues, including embryos, oocytes, and neuroblasts, to determine the role of Augmin in generating microtubules not only in mitosis, but also in specialized cell division, and during cell differentiation.

Before joining the Wakefield lab, I did my masters with Dr. Graham Dellaire at Dalhousie University, Halifax, Canada.  My research project was on the regulation of promyelocytic leukemia protein phosphorylation, and its interaction with other proteins, in the DNA damage response pathway.

My special skills include being quasi-ambidextrous and able to fence with either hands, and being a pundit at cracking eggcellent jokes.