Close
Supervisors:
Giovanni Baranello and Naresh Hanchate
Project Description:
SMA type 1 (SMA1) is the most common and severe form of SMA with symptoms onset within the first months of life which include breathing difficulties and movement problems. The extended survival of treated SMA1 children is enabling us to appreciate neurodevelopmental phenotypes that were not seen before, as untreated patients did not generally survive beyond the age of two. We are now observing that a high proportion of treated SMA1 patients exhibit developmental delay and speech-communication difficulties.
In our lab we have two SMA transgenic mouse models which we treat with two of the available therapies (a small molecule and an antisense drug). Our aim is to investigate the expression of SMN transcripts and protein levels in brain tissue before and after treatment, comparing wildtype and SMA mice, as well as investigating how these levels change with age.
This project aims to investigate the development expression of the SMN protein, primarily in the brain of two mouse models of Spinal muscular atrophy (SMA), a rare genetic neuromuscular disorder. We are investigating how two different treatments (administrated prenatally and/or postnatally) can rescue the phenotype seen in untreated diseased mice.
The project involves several different techniques such as mouse genotyping using PCR and gel electrophoresis, mouse tissue dissections (brain, spinal cord, muscle) from treated and untreated mice at different ages and protein and RNA extraction from these tissues. It also involves western blots and RTqPCR to measure protein and transcript levels, as well as immunohistochemistry to study markers of neuronal growth in brain tissue.
Behavioural studies will be carried out to investigate social interactions of untreated versus treated mice as well as investigating the deletion of SMN gene in specific cell types using a Cre-Lox system in mice.
Contact Information:
g.baranello@ucl.ac.uk