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  Prof Caroline Brennan, Dr Chema Martin, Dr Maxim Freydin  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

  • Supervisors: Prof Caroline Brennan, Dr Chema Martin and Dr Maxim Freydin
  • Funding: QMUL Principal's Studentship
  • Deadline: 31st January 2023

Research environment

The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 180 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.

The project is a collaboration between 3 groups: The Brennan lab consists of 5 PhD students, a PDRA and a research technician, all of whom use zebrafish as a model system to address aspects of behavioural neuroscience; The Martin lab consists of 5 PhD students and 2 PDRA looking at genomic regulation of early embryonic development. The Freydin lab uses genetic epidemiology, statistical genetics and bioinformatics applied to large population datasets to decipher molecular bases of complex human diseases

Training and development

Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.

Project specific training will include genetic epidemiology and bioinformatics, zebrafish behavioural and developmental analysis including immunohistochemistry and in situ hybridisation, analysis of transcriptome via RNASeq, basic molecular biology techniques, and CRISPR/cas9 gene editing.

Project description

Impulsivity is associated with psychiatric disease. Impulsivity also impacts decision making for healthy individuals and is associated with poorer educational achievement, and with mal-adaptive internet use(1-5). Impulsivity is highly heritable with over 500 loci showing significant association with impulsivity traits in a healthy population(6). However, we currently have limited understanding of how these genetic variants contribute to behavioural outcomes.

We recently completed a screen of ENU mutagenized zebrafish and identified several families showing heritable increases in impulsivity. Here we build on these results combining gene expression data from human and animal (zebrafish) studies and generation of targeted zebrafish mutants to gain mechanistic insight into neural pathways and cell biological processes underlying individual differences in impulse control. Using human data and leveraging novel multivariate genomic methods (i.e., Genomic Structural Equation Modelling) we create a refined and empowered multivariate genome wide association study (GWAS) for impulse control.

We then subject summary statistics from the GWAS to gene-set analysis to identify biological pathways involved. Transcriptome wide association study based on our multivariate GWAS summary statistics will be used to infer gene expression changes associated with impulsivity using brain eQTL summary statistics. Differentially expressed gene sets from human analysis will be combined with RNAseq data from mutant lines of zebrafish that show deficits in impulse control. All gene sets will be assessed for pathway enrichment and examined for similarities using multivariate statistics and machine learning.

We use CRISPR/cas9 gene editing to generate targeted loss of function mutants in candidate genes selected from our pathway analysis. Behavioural and cell biological analysis of mutant lines at developmental and adult stages will be used to test causality and hypotheses regarding mechanism of action of identified candidate genes. The results of our work has the potential to inform pharmacological and non-pharmacological treatment of impulsivity disorders or lead to the development of interventions to improve life outcomes and prevent progression to maladaptive behaviours in the healthy population.

Funding

The studentship is funded by Queen Mary and will cover home tuition fees, and provide an annual tax-free maintenance allowance for 3 years at the UKRI rate (£19,668 in 2022/23).

For international students interested in applying, please note that this studentship only covers home tuition fees and students will need to cover the difference in fees between the home and overseas basic rate. Tuition fee rates for 2023-24 are to be confirmed. Details on current (2022-23) tuition fee rates can be found at: https://www.qmul.ac.uk/postgraduate/research/funding_phd/tuition-fees/

Eligibility and applying

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree or a masters degree in an area relevant to the project (biological sciences, genetics, genomics, behavioural neuroscience, psychology). 

Basic understanding and experience in statistical and data analysis would be an advantage, but not essential.

Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our English language requirements page for details: https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/

Informal enquiries about the project can be sent to Caroline Brennan at [Email Address Removed]. Formal applications must be submitted through our online form by 31st January 2023.

The School of Biological and Behavioural Sciences is committed to promoting diversity in science; we have been awarded an Athena Swan Silver Award. We positively welcome applications from underrepresented groups.

http://hr.qmul.ac.uk/equality/

https://www.qmul.ac.uk/sbcs/about-us/athenaswan/

Apply Online


Funding Notes

The studentship is funded by Queen Mary and will cover home tuition fees, and provide an annual tax-free maintenance allowance for 3 years at the UKRI rate (£19,668 in 2022/23).
For international students interested in applying, please note that this studentship only covers home tuition fees and students will need to cover the difference in fees between the home and overseas basic rate. Tuition fee rates for 2023-24 are to be confirmed. Details on current (2022-23) tuition fee rates can be found at: https://www.qmul.ac.uk/postgraduate/research/funding_phd/tuition-fees/

References

1) Dickman, S. J. Functional and dysfunctional impulsivity: personality and cognitive correlates. J Pers Soc Psychol 58, 95 (1990).
2) Martin, L. E. & Potts, G. F. Impulsivity in decision-making: An event-related potential investigation. Pers Individ Dif 46, 303–308 (2009)
3) Wittmann, M. & Paulus, M. P. Decision making, impulsivity and time perception. Trends Cogn Sci 12, 7–12 (2008)
4) Franken, I. H. A., van Strien, J. W., Nijs, I. & Muris, P. Impulsivity is associated with behavioral decision-making deficits. Psychiatry Res 158, 155–163 (2008).
5) Merrell, C. & Tymms, P. B. Inattention, hyperactivity and impulsiveness: Their impact on academic achievement and progress. British Journal of Educational Psychology 71, 43–56 (2001).
6) Karlsson Linnér, R. et al. Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction. Nat Neurosci 24, 1367–1376 (2021)
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