De-risking PWS drug development through preclinical screening
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: School of Medicine
Abstract
Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder in which individuals display behavioural and psychiatric problems. It is caused by loss of expression, either through deletion or abnormal epigenetic regulation, of a number of normally paternally expressed imprinted genes. Working with the Foundation for Prader-Willi Research Pre-clinical Animal Network (FPWR-PCAN), the aim of this project is characterise new PWS mouse models & standardise a pre-clinical screening platform for drug candidates [1]. We will use a number of behavioural paradigms established in our lab to assess activity, sensory-motor gating, learning and memory, and other aspects of cognition in two mouse models for PWS [2-4]. Specifically, an existing Snord116-ko mouse model [5,6] and a newly generated Ipw-ko model. In addition, we will be performing some molecular analyses using the novel Ipw-ko mouse, based on previous observations of interactions of this non-coding RNA with the regulation of a separate cluster of imprinted genes containing the non canoncial Notch-ligand, DIk1 [7]. Parallel characterisation of these two models will allow us to delineate the relative contribution of each gene to the overall PWS phenotype and therefore aid the developmentof targeted therapeutics.
Organisations
People |
ORCID iD |
Anthony Isles (Primary Supervisor) |
Publications
Isles A
(2022)
The contribution of imprinted genes to neurodevelopmental and neuropsychiatric disorders
in Translational Psychiatry
Zahova S
(2018)
The Role of the Prader-Willi Syndrome Critical Interval for Epigenetic Regulation, Transcription and Phenotype
in Epigenomes
Zahova SK
(2021)
Comparison of mouse models reveals a molecular distinction between psychotic illness in PWS and schizophrenia.
in Translational psychiatry
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/R502340/1 | 30/09/2017 | 29/09/2021 | |||
1976193 | Studentship | MR/R502340/1 | 30/09/2017 | 30/03/2021 |
Description | Travel award from the Guarantors of Brain |
Amount | £850 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2019 |
End | 11/2019 |
Description | Brain Domain |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Postgraduate students in my team created a blog where topics of neuroscience are explained in laymen terms. The idea is to spread scientific knowledge in an entertaining and relatable way. |
Year(s) Of Engagement Activity | 2017,2020 |
Description | Pint of science |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | I was part of the local team for the international science festival Pint of Science. We organized three evenings of different topics within neuroscience. Scientists were invited to speak to the general public about their research in a pub. We had upwards of a hundred attendees over the three nights. |
Year(s) Of Engagement Activity | 2017,2018 |