Research Interests D R . R U B E N C A U C H I
Motor Neuroscience and Functional Genetics
Motor neuron disease is characterised by weakness and wasting of voluntary
muscles responsible for crawling, walking, neck control and swallowing.
Muscle atrophy is thought to arise from the selective degeneration of motor
neurons.
Several proteins with a causal role in motor neuron disease are expressed in
every cell of the body to perform a crucial ‘housekeeping’ role. A case in
point is the survival motor neuron (SMN) protein, which is the determining
factor of the childhood motor neuron disease Spinal Muscular Atrophy (SMA).
SMA is the most common genetic cause of infant mortality and the second
most common lethal, autosomal recessive disease after cystic fibrosis.
SMN partners with Gemins 2-8 and UNRIP to form a complex that is
responsible for a vital cellular function: assembly of small nuclear
ribonucleoproteins
(snRNP),
which
are
the
building
blocks
of
the
spliceosome. The spliceosome is the cellular machine that carries out premRNA splicing, i.e. removal of introns and ligation of exons and hence its
function is essential for generating mature versions of mRNAs that can be
readily translated into functional proteins.
My lab’s research attempts at answering why reduced SMN levels
experienced
by
SMA
neuromuscular tissue.
patients
has
a
catastrophic
impact
on
only
Is it possible that the SMN complex has a
neuromuscular-specific function that is independent of snRNP assembly?
Does missplicing have a major negative impact on motor neurons and/or
muscle relative to non-neuromuscular tissues? Could both or either of these
hypotheses be true?
We exploit the rich and powerful genetic toolbox of the fruit fly Drosophila
melanogaster to investigate these key questions.
In view of the
extraordinary degree of genetic and physiological conservation to humans,
the fly is regarded as an excellent animal model of neurodegenerative
disease.
Needless mentioning, several landmark discoveries in flies were
elevated to a Nobel Prize (1933 - Thomas H. Morgan; 1946 - Hermann J.
Muller; 1995 - Edward B. Lewis, Chistiane Nusslein-Volhard & Eric F.
Wieschaus; 2011 – Jules A. Hoffmann).
In assessing the function of the SMN-Gemin complex we make use of
genetic, molecular biology, immunofluorescent imaging and biochemistry
techniques as well as behavioural studies.
We believe that a better
understanding of the functions of the SMN complex will inform the
development of curative therapeutics for SMA.
For further information on my research and academic activities please consult my
university website: http://staff.um.edu.mt/ruben.cauchi