Project 44.2: Deciphering mechanisms and biomarkers of autism through mutations in the SHANK3 gene: A Translational approach
Lead Research Organisation:
King's College London
Department Name: Forensic and Neurodevelopmental Science
Abstract
Autism is a pervasive neurodevelopmental syndrome characterized by deficits in social reciprocity and
communication, and presence of repetitive behaviours. Given the worldwide increase in autism, effective
interventions are urgently needed. This is however hampered by our poor understanding of causal
mechanisms, mainly due to autism's heterogeneity in aetiology. In that respect, single-gene forms of
autism, such as the Phelan McDermid Syndrome (PMS) caused by a mutation in the SHANK3 gene, are
better suited to elucidate the pathophysiology of autism.
In our translational research, human and rodent studies are combined to elucidate the neurobiological
underpinnings of autism. We offer a PhD opportunity to join our team and work with humans and rodents
to examine the biology associated with SHANK3 gene mutations. We use MRI as a translational tool to
examine the brain structure, function and biochemistry. We aim to define the brain systems involved in
PMS/autism in our patient populations and then establish whether these signatures can be recapitulated
in rodents carrying the same mutation. This back-translation into animal models coupled with cutting-
edge methods (e.g. 3D imaging in transparent brains (CLARITY), optogenetics, electrophysiology) will
allow us to confirm the cellular basis of brain deficits and generate novel treatment targets. In the first
year the student will learn technical skills and begin to acquire MRI data. In the second and third years,
they will examine in more detail the neurobiology of SHANK3 mutation. This multidisciplinary project
provides an outstanding array of skills and a potential to rapidly impact upon our understanding of autism.
communication, and presence of repetitive behaviours. Given the worldwide increase in autism, effective
interventions are urgently needed. This is however hampered by our poor understanding of causal
mechanisms, mainly due to autism's heterogeneity in aetiology. In that respect, single-gene forms of
autism, such as the Phelan McDermid Syndrome (PMS) caused by a mutation in the SHANK3 gene, are
better suited to elucidate the pathophysiology of autism.
In our translational research, human and rodent studies are combined to elucidate the neurobiological
underpinnings of autism. We offer a PhD opportunity to join our team and work with humans and rodents
to examine the biology associated with SHANK3 gene mutations. We use MRI as a translational tool to
examine the brain structure, function and biochemistry. We aim to define the brain systems involved in
PMS/autism in our patient populations and then establish whether these signatures can be recapitulated
in rodents carrying the same mutation. This back-translation into animal models coupled with cutting-
edge methods (e.g. 3D imaging in transparent brains (CLARITY), optogenetics, electrophysiology) will
allow us to confirm the cellular basis of brain deficits and generate novel treatment targets. In the first
year the student will learn technical skills and begin to acquire MRI data. In the second and third years,
they will examine in more detail the neurobiology of SHANK3 mutation. This multidisciplinary project
provides an outstanding array of skills and a potential to rapidly impact upon our understanding of autism.
Organisations
People |
ORCID iD |
Declan Murphy (Primary Supervisor) | |
Willi Cosima (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013700/1 | 01/10/2016 | 30/09/2025 | |||
2290735 | Studentship | MR/N013700/1 | 01/10/2019 | 01/04/2023 | Willi Cosima |