Investigating the therapeutic potential of newly identified gene targets using stem cell models of human neurodegenerative disease

Lead Research Organisation: University of Bristol
Department Name: Clinical Science at South Bristol


Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD)) are characterised by abnormal protein
metabolism1, 2 and mitochondrial impairment and dysfunction also accrues with age in these diseases3. We have used an in
vitro model that recapitulates the damage to mitochondria that occurs during neurodegenerative illnesses to carry out a highthroughput
screen of 7500 genes. We have recently completed a secondary screen and identified thirty druggable genes
(can be pharmacologically manipulated) whose role in neurodegenerative disease we wish to investigate further. These
genes fall into three broad classes, those that regulate: protein degradation pathways; free radical levels; DNA repair and
Therapeutic targets will be characterised and their therapeutic potential assessed in collaboration with Takeda UK using
human neuronal cells derived from the induced pluripotent stem cells (IPSC) of patients. We already have IPS cells from
patients carrying G51D, A53T and AST18 (triplication) mutations synuclein gene. Other human disease models are now
available and in addition we have established pharmacological, lentiviral, molecular and biochemical assays5, 6.
Translational focus:
There is very strong translational focus, by the end of the PhD genes that can be targeted to mediate neuroprotection would
have been characterised. Furthermore, senior scientists at Takeda Cambridge will support the student and it is hoped that
pharmacological compounds that can manipulate specific gens/ signalling pathways will be available.
PhD training:
This project offers a unique opportunity for the student to learn molecular (e.g. lentiviral construction, cloning, siRNA/miRNA
mediated gene knockdown, qPCR) imaging (confocal, fluorescent microscopy), biochemical (measurements of proteins,
RNA and DNA, assays of mitochondrial function) and stem cell biology (culturing of neurons derived from human IPS cells
carrying autosomal dominant mutations in genes implicated in Parkinson's disease). In addition they will collaborate with an
industrial partner and gain insight into a drug development program. The student may also gain experience of using genomic
analyses7 and will assess the therapeutic and regenerative potential of the compounds in models of Alzheimer's and
Parkinson's disease.


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Description Assisting at the Bristol University Postgraduate Open Day 2018 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact I assisted with the GW4 MRC BioMed DTP stand at the Bristol University Postgraduate Open Day in November 2018. The purpose of this was to advertise to and provide information for potential applicants for the DTP. I was able to speak to many prospective applicants to encourage applications to the programme, and to discuss my own experiences of carrying out a PhD funded by this DTP. This involved acting as an ambassador for the DTP by discussing my research area and answering various questions about the DTP and the University department.
Year(s) Of Engagement Activity 2018
Description Research Revealed: Brains (Live Lab with We The Curious for Brain Awareness Week) 
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 volunteered with We The Curious (formally At Bristol) as an expert volunteer for the Research Revealed: Brains live lab event as part of Brain Awareness Week 2017. This involved speaking to visitors about neuroscience research in general and the research I am conducting currently as part of my PhD. There was a special focus on the use of human brain tissue in research. The purpose was to give visitors (school children, families and the general public) the opportunity to speak to neuroscience researchers first-hand about their research, and to participate in some laboratory activities in a mock neuroscience lab. I was also able to discuss with visitors why people donate their brains for research and how this helps us to work towards developing medicines for neurological diseases. The activity as a whole was evaluated positively by visitors, and I was personally able to engage in discussion about my research with hundreds of visitors over the course of the event. I also spoke to many visitors who expressed that they had increased their understanding of and changed their opinions on brain donation for research as a result of participating in the event
Year(s) Of Engagement Activity 2017
Description Volunteer mentor for The Mullany Fund e-mentoring 1+1 project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact As a volunteer with the Mullany Fund, I worked as an e-mentor with school-aged children who had previously expressed an interest in STEM careers. The purpose of this activity was to enable and encourage access to STEM careers for young people who may have barriers to accessing higher education. I received mentoring training for this post, and was able to mentor the young people by answering their questions related to what it is like working as a researcher. I also provided them with access to various resources to help them learn more about a career in research, and to help them access relevant work experience placements and study tools to increase their chances of accessing higher education. I was able to communicate my research to the mentees, and general feedback indicated that many of the young people who were mentored in the scheme had decided to apply to University as a direct result of the mentoring scheme.
Year(s) Of Engagement Activity 2018