Research Staff

Postdoctoral Researchers

Emma East  E.East@open.ac.uk

Postgraduate Students

Stanley Kimani  S.G.Kimani@open.ac.uk

Melanie Georgiou  M.Georgiou@open.ac.uk

Project Officer

Tina Wardhaugh

Alumni
Miguel Ardid
Dr. Elizabeth Latta

Embryonic nervous system showing
segmented, "striped" appearance

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Multipotent cells in the embryo and stem cells in adults face similar challenges. They need to integrate signals from their environment in order to navigate and make cell fate decisions. These decisions are crucial for generating complex tissue architectures and ordered populations of specialised cells, both during the assembly of an animal in development and by stem cells as they repair/replace tissues in adulthood.
We attempt to understand the signals that allow an undifferentiated precursor/stem cell to determine where it is and where it should be going, and what it is and what it should become.

Cranial neural crest cells are multipotent precursors that migrate from the hindbrain neural tube to generate the cartilaginous structures of the jaw and face, pigment cells of the skin, and much of the cranial peripheral nervous system. The migration of cranial neural crest cells is patterned into a series of cell streams, with intermediate crest-free zones. The hindbrain is similarly patterned into a series of segmented units, called rhombomeres (r), and is an obvious candidate source of neural crest patterning information.

Neural Crest Migration
Time-Lapse

Lineage marking of crest populations

ErbB4 signaling in r3 maintains the adjacent neural crest-free zone.
Loss of ErbB4 causes misrouting of r4 crest cells alongside r3

We study the mechanisms that maintain the segregation of cranial neural crest cell streams, ensuring that these cells get to their appropriate destinations in the developing head. Our work is aimed at understanding the identity of the neural crest patterning cues and how this information is transferred from the rhombomeres to the adjacent mesenchyme. We have found that patterning cues, important for maintaining the crest-free zone adjacent to r3, are provided by the receptor tyrosine kinase ErbB4 within r3 (see panels, above right). We have also found that cranial surface ectoderm is an independent source of information for patterning cranial neural crest cell migrations. How these two signaling modes interact is an ongoing topic of our research.

Neural crest can differentiate into neurons.
A major strand of our research involves developing a better understanding of the factors that dictate the position and regulate the size of clusters of placodal and neural crest-derived neurons (ganglia) as they form within the developing head.
For this work we temporarily modify gene expression within selected populations of crest cells, or chemically modify signal transduction pathways.
This highly-skilled work is done by Liz and is unveiling novel perspectives on the molecular and cell-dynamic bases of several human congenital cranio-facial abnormalities. This work benefits enormously from the excellent microscopy and imaging facilities available at the Open University.

(Left) A hotbed of neurogenesis.
As the nervous system begins to form, neurons in the vestibulo-acoustic ganglia of a chick embryo can be traced in 3-D by examining a series of confocal images of anti-neurofilament immunostaining.
Move your pointer over the image to play the animation.

We are investigating the potential of transplanted adult neural crest stem cells to home to sites of brain injury. Our current data indicates that these cells home to injury sites and could be used for autologous stem cell therapy, either for neural repair or to deliver gene products. This work is in collaboration with colleagues at Imperial College London and is funded by the Medical Research Council.
In other work, involving Mark Hirst and Kerry Murphy, Tina is investigating the biology of adult stem cells in the progressive and fatal neurological condition, Huntington's disease.

(Right) MRI scans showing the progressive migration of transplanted adult neural crest cells (dark label in top panel, initially within the ringed areas) towards a focal brain injury (white arrow). Neurohistological analyses (D and E) confirm the migration of pre-labelled green neural crest stem cells to the injury site and their differentiation into appropriate CNS cell types (red label in D).

Selective targeting to cancerous cells of a novel PDT photo-sensitizer.

Many of the same molecular pathways that my group studies during development become dysregulated in tumours. In a collaborative venture between Jon Golding and James Phillips in Life Sciences, James Bruce in Chemistry, and clinical colleagues at University College London, we are developing a series of 3rd generation photodynamic therapy drugs, with improved selectivity for cancerous cells. Early work on this project by Miguel is now being perfected and expanded in several new and exciting directions by Stanley.

Localised PDT destruction of sensitized cancer cells.

We are developing advanced 3-dimensional culture models of PNS and CNS lesions to better understand the complex cellular interactions that occur at sites of nerve injury and hinder regeneration. Additionally, we are using our 3D culture models to explore the potential of various adult stem cells to assist in the repair of adult nervous system lesions. Aspects of this work are currently funded by the Wellcome Trust and represent collaborative ventures between many colleagues at the Open University; notably the groups of James Phillips, Jane Loughlin and Jill Saffrey. This work is being done by Emma and you can discover more by following this link for the latest information

Jon, discussing our stem cell work with Colin Blakemore, the (then) Chief Executive of the Medical Research Council

What's happening in Milton Keynes?
MK Web,  Xscape,  The Centre:MK


Science Faculty Research


YES!, we do research at the OU.
Research Highlights 2009/10 (PDF).

If you're interested in postgraduate
or post-doctoral research at the
Open University, then please get in touch.

Work in the lab is currently funded by:
Wellcome Trust (£ 200,000)
Open University (£ 70,000)

Recent previous funds include:
Medical Research Council
(£ 171,700)
Open University (£ 10,000)

Developmental Biology web sites:
ISDB
Developmental Biology Online

Selected Journals:
Development
Stem Cells

Translational medicine web sites:
Spinal Research Trust
London Technology Network

How well do you know the OU? (YouTube)
Open University on iTunesU
Prestigious OU Life Sciences alumni

Click here to check out a selection of photos of our labs and MK life

All Publications