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2022-23 Bloomsbury PhD Studentships

The Bloomsbury Colleges group was set up in 2004 and consists five institutions: Birkbeck, London School of Hygiene & Tropical Medicine (LSHTM), the Royal Veterinary College (RVC), the School of Oriental and African Studies (SOAS), and the UCL Institute of Education (UCL–IOE). These studentships were set up to increase collaboration and interdisciplinary research opportunities across the colleges.

Applications are invited for three-year PhD studentships, to start in the academic year 2022-23. There are two studentships available at the London School of Hygiene & Tropical Medicine (where LSHTM is the lead institution): one studentship award per research project.

Funding

Each studentship will provide

for the duration of the award.

Projects

The LSHTM-led studentship projects available for 2022-23 are:

Investigating the Role of the Methyl Citrate Cycle in Mycobacterial Energy Metabolism and Potential Value as a Novel Target for Antimicrobial Inhibition

Supervisory team

Project description

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex, is a disease of global importance1. TB remains the leading cause of death from any single infectious pathogen, and despite control efforts, there is rising incidence of multi-drug resistance (MDR). Furthermore, non-tubercular mycobacterial (NTM) species are a significant cause of opportunistic infection. New insight is required into the fundamental microbiology of these pathogens to reveal novel targets for the next generation of antimicrobials.

The methyl citrate cycle (MCC) is an understudied metabolic pathway that contributes to energy metabolism in the human pathogen, Mycobacterium tuberculosis (MTB)2. The pathway is responsible for the beta-oxidation of odd-chain length fatty acids as well as certain amino-acids. Preliminary mutagenesis studies have suggested that the key enzymes involved in the MCC (methylcitrate dehydratase; methylcitrate synthase) are essential for the growth of the bacteria on cholesterol, and in bone-marrow derived macrophages3. The pathway is also required for the detoxification of propionate.

Targeting energy metabolism in MTB has been shown to be a highly effective strategy, and given rise to the first newly approved antibiotic with a unique mode of action against MTB in decades, namely bedaquiline (BDQ)4. While BDQ rapidly inhibits the ability of the bacteria to generate new ATP via the electron transport chain, ATP can still be generated, less efficiently, through recycling of ADP by central carbon metabolism. Recently published studies have shown that treatment with BDQ remodels central metabolism in MTB, increasing its dependency on glycolysis and downstream pathways including the glyoxylate and methylcitrate cycles4. This is the first indication that the MCC may serve a dual purpose as an AMR mechanism. We seek to understand the conditional essentiality of the MCC under different physiological conditions, including antimicrobial stress, and assess its role as a metabolic escape route for tolerating disruption to bioenergetics.

The project will study the transcriptional and metabolic response of MTB under these different conditions, and test the contribution of the MCC through CRISPRi mediated silencing of the key enzymes of the MCC. We will determine the value of potential inhibitors of the MCC alone, and in combination with existing antimicrobials that target other aspects of energy metabolism, including the ATP synthase apparatus and the electron transport chain. Finally, we will consider the contribution of the MCC to broader ATP-dependent functions including efflux and secretion systems, which have been linked with drug resistance and virulence, respectively.

The PhD project will primarily be based at LSHTM (Dr S Willcocks) and will include training in molecular biology and microbiology, including the handling of MTB in BSL3 containment. Birkbeck Department of Biological Sciences (Prof S Bhakta) is a leading centre of expertise in structural and molecular mycobacteriology research, focussing on gaining insights into biological processes that cause human disease, to validate novel therapeutic targets. Mycobacteria Research Laboratory focuses on discovering novel targets in M. tuberculosis and collaborates on the development of new chemical entities to fulfil the major chemotherapeutical need for TB disease. Exposure to the applied biological and translational research at Birkbeck will lead to advanced biological skills, including aspects of the functional biology of mycobacteria. The student will also be exposed to the world-class research in infectious disease undertaken in a multidisciplinary setting, with a particular strength in TB. Upon completion of the PhD it is anticipated that candidate will have good depth of skills across multiple disciplines, including microbiology, molecular biology, genetics, and bioinformatics, making them an attractive prospect for post-doctoral research funding.

Subject areas / keywords

Mycobacterium tuberculosis; antimicrobial resistance; drug discovery; methyl citrate cycle; target validation.

Key references

  1. Gupta, A. et al (2012) Mycobacterium tuberculosis: immune evasion, latency and reactivation. Immunobiology 217(3): 363-74.
  2. Dolan S et al (2018). Loving the poison: the methylcitrate cycle and bacterial pathogenesis. Microbiology. 164:251–259
  3. Munoz-Elias et al (2006). Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Microbiol. 60(5):1109-22
  4. Mackenzie J et al (2020) Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis. Nature Communications. Article number: 6092

Eligibility requirements

Graduates with a good first degree and/or Master’s degree in a relevant subject and with an interest and aptitude for microbiology are encouraged to apply. Previous wet laboratory experience will be valued highly. A prowess for conceptual thinking is desirable.

Further information

Further details about the project may be obtained from:

Principal Supervisor: Dr Sam Willcocks (sam.willcocks@lshtm.ac.uk)

Co-Supervisor: Professor Sanjib Bhakta (s.bhakta@bbk.ac.uk)

Deadline for applications

The deadline for applications is 23:59 (GMT) on Sunday 6 March 2022.

Shortlisted applicants will be invited for interview Monday 21 March 2022.

Assessing adolescent health and wellbeing in Zimbabwe: economic analysis of Y-Check, a novel check-up strategy

Supervisory team

Project description

Improving adolescent health and wellbeing will contribute to the achievement of Sustainable Development Goal 3 ‘ensure healthy lives and promote well-being for all at all ages’. Y-Check is an innovative strategy for health check-up visits during adolescence in low and middle-income countries (LMICs). The approach is innovative and novel, because, in most LMICs, including Zimbabwe, few adolescents have any promotive or preventive contacts with the health system. The strategy will involve the screening and treatment/referral adolescents for common conditions through health check-up visits in younger (10-13y) and older (16-19y) adolescents. Adolescents will only be screened for conditions with an accurate and acceptable test and a locally-accessible effective intervention e.g. mental health, HIV, vision and hearing, anaemia. The following definition of adolescent wellbeing has been proposed ‘Adolescents thrive and are able to achieve their full potential’ (Ross DA et al, JoAH 2020). The effectiveness and cost-effectiveness of the intervention will be evaluated through a prospective intervention study in 4 communities, up to 6 primary schools, and up to 8 secondary schools in Chitungwiza, Zimbabwe. The Y-Check study in Zimbabwe is funded through a UKRI-funded Future Leaders fellowship to Aoife Doyle (Feb 2021- Jan 2025) and a Fondation Botnar multi-country study of adolescent check-up visits coordinated by WHO, Geneva (2022-2024).

The proposed PhD project is an economic analysis of this novel complex intervention aimed at improving adolescents’ wellbeing and academic achievement (Y-Check). The successful PhD candidate will develop and test new methods to measure and evaluate the impact Y-Check and will assess its cost-effectiveness.

The project will build on extensive previous work led by Giulia Greco on adapting, developing and testing wellbeing measures for use in economic evaluations of complex interventions, and on previous work by John Jerrim on the measurement of academic achievement.

Subject areas / keywords

  • Health economics
  • Psychometrics
  • Economic evaluation
  • Education evaluation and assessment
  • Adolescent health and wellbeing
  • Mixed methods

Key references

  • Chingono RMS, Mackworth-Young CRS, Ross DA, Tshuma M, Chiweshe T, Nyamayaro C, Sekanevana C, Doyle AM, Weiss HA, Kohl K, Mangombe A, Madzima B, McHugh G, Ferrand RA. Designing Routine Health Checkups for Adolescents in Zimbabwe. J Adolesc Health. 2021 Aug 3:S1054-139X(21)00342-6. doi: 10.1016/j.jadohealth.2021.07.002. Epub ahead of print. PMID: 34362647.
  • Doyle, A.M., Mchunu, L., Koole, O. et al. Primary healthcare and school health service utilisation by adolescents and young adults in KwaZulu-Natal, South Africa. BMC Health Serv Res 19, 905 (2019) doi:10.1186/s12913-019-4559-2
  • Ross, I., Greco, G., Opondo, C., Adriano, Z., Nala, R., Brown, J., Dreibelbis, R., & Cumming, O. (2021). Measuring and valuing broader impacts in public health: Development of a sanitation-related quality of life instrument in Maputo, Mozambique. Health Economics, 1– 15. https://doi.org/10.1002/hec.4462
  • Greco G, Lorgelly P, Yamabhai I (2016) Outcomes in economic evaluations of public health interventions in LMICs: health, capabilities and subjective wellbeing, Health Economics; 25 Suppl 1:83-94 https://doi.org/10.1002/hec.3302
  • Verfürden, M., Harron, K., Jerrim, J., Fewtrell, M., & Gilbert, R. (2020). Infant formula composition and educational performance: a protocol to extend follow-up for a set of randomised controlled trials using linked administrative education records. BMJ Open, 10 (7), e035968. doi:10.1136/bmjopen-2019-035968
  • Jerrim, J. P. (2018). Inequity and Excellence in Academic Performance: Evidence From 27 Countries. American Educational Research Journal. doi:10.3102/0002831218760213

Deadline for applications

The deadline for applications is 23:59 (GMT) on Sunday 6 March 2022.

Further information

For any queries regarding the project please contact Dr Giulia Greco at: Giulia.Greco@lshtm.ac.uk, copying in Dr Aoife Doyle at: Aoife.Doyle@lshtm.ac.uk.

For details of studentships available at other Bloomsbury colleges but in collaboration with the London School of Hygiene & Tropical Medicine, please see the Bloomsbury Colleges website. Please apply directly to the lead institution only.

Eligibility

Applicants must meet minimum LSHTM entry requirements. Additional requirements may be required for each project. Please see the specific project information for further details.

These studentships are open to applicants assessed as both ‘Home’ and ‘Overseas’ fee status. For further information about Fee Status Assessments please see the School’s policy and procedure document.

Successful applicants who are nationals of, and residents in, low income countries and lower middle income countries (LLMICs) may be eligible for an LSHTM bursary to cover the fee top up costs. LLMIC applicants who are short-listed for interview, will be contacted by the LSHTM Scholarships Team at that time to provide further details of the LSHTM bursary scheme for entry in 2022-23.

Successful international applicants who are not from an LLMIC will be required to cover the tuition fee top up costs from other sources (e.g. other scholarship or bursary awards). Awardees may not use their Bloomsbury studentship stipend or personal funds to top up fees.

To apply

Information about the MPhil/PhD programme structure at LSHTM, as well as application guidance and a link to the portal, can be found on the School’s Research Degrees and Doctoral College pages.

To apply for this studentship, applicants should submit an application for research degree study via the LSHTM application portal. The applicant should apply via the Faculty of the Primary Supervisor for their proposed project. ‘2022-23 Bloomsbury PhD Studentship’ must be entered under the ‘Funding Section’ on the application. Students should submit a research proposal based on the advertisement for this project.

Incomplete applications will not be considered for this studentship.

Applications for this project will only be reviewed and processed after the deadline. All applications that are submitted before the deadline will be considered equally, regardless of submission date.

By submitting an application for this funding applicants agree to its terms and conditions.

Deadline

The application deadline for both projects is 23:59 (GMT) on Sunday 6 March 2022. Please see the specific project information for further details.