2024 BNA Scholars announced
15th March 2024
I. Scientific excellence
Alzheimer’s disease (AD) is the major form of dementia, and memory loss is its main symptom. Recently, the protein REST has been strongly implicated in AD by a high-profile study, revealing high REST brain levels in healthy elderly individuals but not in AD. The supervisor of this project has previously generated a conditional knockout (cKO) mouse model lacking REST in the brain.
II. Clear aim and hypothesis
Enhancing REST function might combat cognitive decline in AD. This project aims to take the next steps in this direction by using brain tissue from REST cKO and control mice and by computational approaches.
III. Methodology and innovations
Brain tissue already collected from REST cKO and control mice and stored at -80°C will be used for the following experiments:
1. Genomics
RNA-Seq analysis of global (whole-genome) gene expression
2. Epigenetics
a) Study of DNA-protein interactions in gene promoters by chromatin immunoprecipitation (ChIP)
b) ChIP-Seq analysis of global DNA binding
3. Biochemistry
Western blot analysis for the NMDA receptor subunits GluN2A and GluN2B
4. Histology
a) Golgi staining
b) Immunohistochemistry for ?-amyloid and phosphorylated Tau
5. Computational modelling
Molecules potentially enhancing REST function will be designed by computational modelling (the 3D structure of REST is already known).
IV. Strategic relevance
This project aligns very well with the strategic priorities of the DTA3 programme and those of the University of Central Lancashire, for the following reasons:
a) It is strongly related to a global health issue, dementia, and to the promotion of healthy ageing
b) It belongs to a key research theme of the University, Neuroscience
c) It will address important scientific questions for a protein strongly implicated in healthy ageing (at high levels) and AD (at low levels)
d) It will strongly involve collaboration and mobility
V. Interdisciplinarity and fit with relevant DTA programme
This project fits very well with the DTA programme of Applied Biosciences for Health (Healthy Ageing), as described above, and is highly interdisciplinary, involving a wide variety of research fields/methods:
1. It is related (and will be combined with, upon publication) to knockout mouse generation
2. It will use various epigenetic, biochemical and histological methods, including elaborate whole-genome analyses
3. It will include computational modelling, a very different type of approach, with strong complementarity with the other experiments and significant pharmaceutical potential arising from the resulting combination
Applicants must apply using the online form on the University Alliance website at https://unialliance.ac.uk/dta/cofund/how-to-apply-2/. Full details of the programme, eligibility details and a list of available research projects can be seen at https://unialliance.ac.uk/dta/cofund/
The final deadline for application is Monday 8 October 2018. There will be another opportunity to apply for DTA3 projects in the spring of 2019. The list of available projects is likely to change for the second intake.
DTA3/COFUND participants will be employed for 36 months with a minimum salary of (approximately) £20,989 per annum. Tuition fees will waived for DTA3/COFUND participants who will also be able to access an annual DTA elective bursary to enable attendance at DTA training events and interact with colleagues across the Doctoral Training Alliance(s).
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 801604.