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As the worldwide genome sequencing project nears completion,
the emphasis in the post-sequencing era will shift to understanding
biological networks: ie, the mechanisms and functional consequences
of genetic interactions. Understanding gene function holds the
best long-term promise for the rational design of selective reagents
to interfere with the abnormal gene function that results in cancer.
This research is the prerogative of basic biological science and
since many of the genes that are disrupted or dysregulated in
cancer are regulators of developmental and differentiation processes
this programme of work is likely to provide significant insight
into cancer mechanisms. The overall strategy is to pursue basic
research into normal developmental and differentiation processes
and gain insight into the underlying mechanisms at the level of
gene expression and also chromatin structure. We particularly
focus on pathways, systems or processes with obvious cancer relevance.
Thus in 1997, the Institute
of Cancer Research established a Section of Gene Function
and Regulation to take on this challenge. The section was chaired
by Tariq Enver until June 2003 and includes
four other faculty members, namely Joan
Boyes, Mike Jones, Amanda
Swain and Ludovica
Bruno.
The scientific activity of the Institute of Cancer Research's
Chief
Executive, Peter Rigby, is also
contained within the Section.
The Section of Gene Function and Regulation is housed in brand
new purpose built space complete with state of the art facilities
in the Institute of Cancer Research's Chester Beatty Laboratories
in London.
Highlights of 2002
A key highlight of 2002 has been the identification and preliminary
characterisation of a candidate population of stem cells present
in mouse and also human breast tissue. This work developed
as a collaborative venture between haematopoietic stem cell
scientists in the section of GFR and scientists’ working
in the Breakthrough Breast Cancer Research Centre. Whilst
at an early stage, these findings are of significant
importance
because the stem cell compartment of tissues is widely considered
to be the ‘target’ in cancer. Thus an understanding
of the stem cell biology of the breast should provide insight
into the origins and development of breast cancer and provide
a framework in which to start to identify ‘cancer’ stem
cells in this tissue.
Also worthy of note this year has been the continued systematic
dissection of the transcriptional regulation of the skeletal
muscle-determining Myf-5 gene. The most recent instalment in
this complex story is the discovery that the early epaxial enhancer
is essential for the initial expression of Myf-5 but not for
the subsequent phases of myogenesis. This work is leading towards
an understanding of how muscle is specified and thus provides
an important window on rhabdomyosarcoma, a muscle-associated
cancer, predominantly of childhood. Also, the molecular complexities
of gene regulation revealed in these studies are likely to play
out in the transcriptional regulation of other key regulatory
molecules in the human genome.
Future aims
The Section of Gene Function and Regulation's overall research
strategy to gain mechanistic insight into how cell fate decisions
are orchestrated during ontogeny and during differentiation of
adult progenitor and stem cells remains unaltered. The effective
linking of Gene Function and Regulation's basic research programmes
in such a manner as to provide support or insight into more
cancer targeted programmes
remains a key objective. Thus our prostate programme
(Dr. Amanda Swain) is of benefit to activities in the Male Urological
Cancer Research, as is our dendritic cell programme (Dr. Ludovica
Bruno)
to tumour immunological programmes currently being considered
at the Royal
Marsden Hospital. Our early vertebrate development
group (Dr. Mike Jones), through interaction with both the Breakthrough
Breast Cancer Research Centre and the Cancer
Research UK Centre for Cell and Molecular Biology, is providing
insight into the genetic pathways in which key cancer genes
function.
Our aim is therefore to continue to foster these important collaborative
links, and to develop new interactions between our muscle developmental
biology programme (Professor Peter Rigby) and our rhabdomyosarcoma
group in the Section
of Paediatric Oncology (Dr. Kathy Pritchard-Jones), as
well as between our chromatin activation laboratory (Dr. Joan
Boyes)
and groups at The Institute interested in how chromosomes illegitimately
recombine to produce mutated or deregulated loci associated
with
cancer.
The Institute is a charity that relies on voluntary funds. If
you are interested in supporting us please look on The Institute's
Fundraising Page
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Last Modified 23/02/04
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