You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Expected results<br />
The SIROCCO consortium will investigate the stages in<br />
growth, development and disease that are infl uenced by<br />
sRNAs. The project can be considered to have three overlapping<br />
phases. The fi rst is descriptive and will continue<br />
throughout the programme. This phase aims to describe the<br />
full complement of sRNAs in a range of organisms and cell<br />
types and correspondingly to develop a complete understanding<br />
of the proteins that act as enzymes, co-factors and<br />
structural components of the sRNA machinery.<br />
The second phase involves testing the function of sRNAs<br />
and sRNA-related proteins in the basic sRNA mechanisms,<br />
and eventually establishing their role in regulatory networks<br />
through experimental intervention. Genetic and molecular<br />
methods will be used to manipulate the expression of these<br />
components, while biological assays and molecular profi ling<br />
of RNA will be used to assess the role of the targeting<br />
components.<br />
In the third, predictive phase of the programme, the aim will<br />
be to develop rules to describe the behaviour of sRNA systems<br />
as isolated regulatory modules and as part of complex<br />
regulatory networks. Component activities in this phase will<br />
involve the computation of rules and their validation by<br />
experimentation. It will be possible from this phase to design<br />
sRNA mimics of natural sRNAs, and to predict their eff ects in<br />
cells and organisms. It will also be possible to predict the<br />
behaviour of cells or organisms in which the sRNA machinery<br />
is regulated by developmental or external stimuli.<br />
Somite-specifi c expression of miR-206.<br />
Mouse embryo (E10.5) was hybridized to an LNA<br />
oligonucleotides complementary to miR-206.<br />
The blue staining indicates the very specifi c<br />
accumulation of miR-206 in the somites.<br />
(Wheeler G, Valoczi A, Havelda Z, Dalmay T.<br />
In situ detection of animal and plant microRNAs.<br />
DNA Cell Biol. 2007 Apr; 26(4):251-5.)<br />
Potential Application<br />
RNA silencing technology has enormous potential for use as<br />
a therapeutic agent in the treatment of infectious diseases<br />
and for any condition involving the mis-regulation of gene<br />
expression. It is known that diff erent microRNAs can function<br />
as tumour suppressors or oncogenes and that their<br />
expression levels have diagnostic and prognostic signifi -<br />
cance. The role of small RNAs in complex neuropathological<br />
disorders such as schizophrenia and in neurodegenerative<br />
conditions such as Alzheimer’s Disease is being investigated<br />
by members of the SIROCCO consortium. Diagnostic or<br />
therapeutic advances in these areas would have powerful<br />
public health implications.<br />
The SIROCCO consortium aims to understand and exploit<br />
the diversity of sRNA mechanisms. The elucidation of the<br />
genomics of sRNA and of sRNA-based regulation will lead<br />
to novel and fundamental insights into the composite genetic<br />
networks that underlie normal and diseased growth and<br />
development. Achieving these aims will reinforce European<br />
competitiveness in fundamental research and innovation<br />
and will solve important societal problems relating to public<br />
health by improving diagnosis and treatment of diseases.<br />
BIOLOGY 73
Change language