MScR - Determining the genetic and circadian basis of bipolar disorder using Drosophila


   School of Physiology, Pharmacology & Neuroscience

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  Prof J Hodge  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Circadian rhythms and sleep are evolutionarily conserved from fruit flies (Drosophila) and are fundamental as well as vital to biology and health (Jagannath et al., 2017; Menet and Rosbash, 2011). Bipolar disorder is highly heritable with recent genomic studies identifying a conserved set of underlying genes that are also implicated in circadian rhythm and sleep regulation, which are known to be disrupted in the disorders(Franklin and Dwyer, 2021; Harrison, 2016).

These evolutionarily conserved signalling pathways appear to be regulated by mood stabilising drugs (Logan and McClung, 2016; McCarthy et al., 2016; McCarthy et al., 2012). In this project we will generate fly models mutant for genes associated with bipolar disorder and characterise them for circadian rhythms under different light conditions. In parallel we measure the effect on sleep including measuring sleep stages and sleep deprivation, using standard assays set up in the lab(Buhl et al., 2019; Buhl et al., 2020).

To measure behavioural changes related to mood in these different flies, circadian and sleep states, we will use an affective bias assay we have developed for Drosophila (Deakin et al., 2018). We will validate the model by attempting rescue of behavioural deficits by feeding the flies lithium, valproate and other drugs predicted to correct the molecular defects(Dokucu et al., 2005).

If you have questions, please email the supervisor ([Email Address Removed]).

How to apply:

MSc by Research (MScR) is a 1-year research degree that provides an intensive lab-based training and a preparation for PhD study. You will carry out your studies as part of your research group – like a PhD student does. Towards the end of the year, you write up a thesis on your research and are examined on this. This degree suits students wanting to gain maximum research experience in preparation for PhD applications.

We are keen to recruit a diverse range of students and to ensure our research is open to all. We particularly welcome applications from groups traditionally under-represented in life sciences research. Please check the University webpages for the current tuition fee information. Most MScR projects also require a bench fee. This varies depending on the research and your project supervisor can tell you the bench fee for the project.

Please follow the link below and apply to the Faculty of Life Sciences, School of Physiology, Pharmacology and Neuroscience, selecting the programme "Physiology, Pharmacology and Neuroscience (MSc by Research)".

PhD Physiology, Pharmacology and Neuroscience | Study at Bristol | University of Bristol


Biological Sciences (4) Medicine (26)

Funding Notes

This MSc by Research project is available to UK and international students who wish to self-fund their studies or who have access to their own funding.

References

Buhl, E., Higham, J.P., and Hodge, J.J.L. (2019). Alzheimer's disease-associated tau alters Drosophila circadian activity, sleep and clock neuron electrophysiology. Neurobiol Dis, 104507. 10.1016/j.nbd.2019.104507.
Buhl, E., Kottler, B., Hodge, J.J.L., and Hirth, F. (2020). Thermoresponsive motor behavior is mediated by ring neuron circuits in the central complex of Drosophila. Scientific Reports 11, 155. https://doi.org/10.1038/s41598-020-80103-9.
Deakin, A., Mendl, M., Browne, W.J., Paul, E.S., and Hodge, J.J.L. (2018). State-dependent judgement bias in Drosophila: evidence for evolutionarily primitive affective processes. Biology Letters 14.
Dokucu, M.E., Yu, L., and Taghert, P.H. (2005). Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila. Neuropsychopharmacology 30, 2216-2224. 10.1038/sj.npp.1300764.
Franklin, C., and Dwyer, D.S. (2021). Candidate risk genes for bipolar disorder are highly conserved during evolution and highly interconnected. Bipolar Disord 23, 400-408. 10.1111/bdi.12996.
Harrison, P.J. (2016). Molecular neurobiological clues to the pathogenesis of bipolar disorder. Curr Opin Neurobiol 36, 1-6. 10.1016/j.conb.2015.07.002.
Jagannath, A., Taylor, L., Wakaf, Z., Vasudevan, S.R., and Foster, R.G. (2017). The genetics of circadian rhythms, sleep and health. Hum Mol Genet 26, R128-r138. 10.1093/hmg/ddx240.
Logan, R.W., and McClung, C.A. (2016). Animal models of bipolar mania: The past, present and future. Neuroscience 321, 163-188. 10.1016/j.neuroscience.2015.08.041.
McCarthy, M.J., Le Roux, M.J., Wei, H., Beesley, S., Kelsoe, J.R., and Welsh, D.K. (2016). Calcium channel genes associated with bipolar disorder modulate lithium's amplification of circadian rhythms. Neuropharmacology 101, 439-448. 10.1016/j.neuropharm.2015.10.017.
McCarthy, M.J., Nievergelt, C.M., Kelsoe, J.R., and Welsh, D.K. (2012). A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response. PLoS One 7, e32091. 10.1371/journal.pone.0032091.
Menet, J.S., and Rosbash, M. (2011). When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders. Curr Opin Neurobiol 21, 849-857. 10.1016/j.conb.2011.06.008.

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