106728729
UNIVERSITY OF LIVERPOOL
School of Biological Sciences
BBSRC funded Studentship
Using Drosophila and C.elegans models of cell migration to obtain novel insights into normal development and
cancer cell metastasis
Dr D.H. Bennett, daimark.bennett@liverpool.ac.uk and Dr T.K. Kinnunen, T.K.Kinnunen@liverpool.ac.uk
Directed cell migration is critical for normal development and is involved in aberrant processes underlying
various neurological disorders and cancer cell metastasis. Whilst much is known about the movement of single
cells in simple environments, guidance of cells within intact tissues is still poorly understood at the cellular and
molecular level. Better understanding of this process has important potential application to the development of
technologies for the treatment of disorders associated with deregulated cell migration. In recent CRUK-funded
work (2006-2008), we have uncovered a critical role for the Mig-10/RIAM/Lpd (MRL) family of cytoplasmic
adapter proteins in promoting directed cell migration in Drosophila. The focus of the proposed studies is to
dissect the molecular mechanisms of MRL action in Drosophila, and to develop approaches for manipulating
MRL-dependent pathways. Mechanistic insights obtained will also be tested in C.elegans, where a role for the
MRL pathway in directed neuron migration is well established and mutant alleles are available. Approaches that
we develop to modify MRL function could ultimately have applications in preventing the spread of malignant
tumours in cancer patients or promoting recovery from neuronal tissue damage.
The student will: 1) identify molecular cues driving MRL-mediated cell migration during Drosophila
development; 2) use real time imaging to examine the role of MRL proteins during different stages of guided
migration, from initial polarisation to dynamic collective behaviour; 3) develop genetic and chemical genetic
approaches for manipulating MRL function to obtain further mechanistic insights; 4) examine functional
conservation of these mechanisms in neuron migration and axon outgrowth in C.elegans.
Techniques to be used include: state-of-the-art Drosophila and C.elegans genetics (including RNA interference,
FRT/Flp site-directed recombination, Gal4-UAS overexpression); cell biology (immunofluorescence; live
imaging); molecular biology and biochemistry (recombinant DNA techniques, immunoprecipitation, Western
Blotting); chemical genetics (split-luciferase binding assays; application of small molecule libraries).
Training
The student will be embedded within an active research group conducting lab-based molecular genetics,
biochemistry and cell biology research highly relevant to the student’s project. Within the group, several lab
members are working on related projects, and adjacent collaborating labs have additional expertise, giving the
student access to a large set of other workers to gain advice and intellectual input. This project will expose the
student to a wide variety of state-of-the art techniques, including RNAi, live imaging, split-luciferase assays,
which will ensure good career development. Generic skills training will be provided through weekly lab
meetings. These will give the student experience of oral presentation of their work, will expose them to other
research methods and systems and broaden their scientific outlook. The student will also be expected to attend
other seminar series within Liverpool and present their work at a minimum of one international meeting.
References:
Bianco, A., et al. (2007). Two distinct modes of guidance signalling during collective migration of border cells.
Nature, 448, 362-365.
Chang, C. et al. (2006). MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in
response to slit and netrin. Curr. Biol., 16, 854-862.
Legg, J. A., and Mackesky, L. M. (2004). MRL proteins: Leading ENA/VASP to Ras GTPases. Nat. Cell Biol.,
6, 1015-1017
Full details of the projects and supervisors can be viewed by clicking on the titles and names, respectively.
Application by email, indicating the project(s) of interest (and supervisors) in priority order, giving the reasons
for this, together with a c.v. including the names and contact details, together with e-mail addresses, of two
academic referees, should be sent as soon as possible to: Mrs. Linda J. Marsh, Research Support Office, School
of Biological Sciences, The Life Sciences Building, Crown Street, Liverpool L69 7ZB (email:
biolres@liverpool.ac.uk, Fax: 0151 795 5122). Review of applications begins from mid January 2008. Please
indicate where you first saw the project(s) advertised.