Summer Research Lab Experience

Join one of our research teams

You will be a member of one of our research teams, and your work will be an important contribution to the group’s discoveries. Summer research lab experience is an invaluable opportunity to gain hands-on experience in a research group and to get career advice from fellow students and mentors. They are also a great way to meet new people; we are a small, friendly department, located in the heart of London.

Eligibility

Opportunities are funded by a number of learned societies. In order to be eligible for a research bursary from these organisations you must be:

  • Taking an undergraduate science degree
  • Considering research as a career
  • Expecting to achieve a First Class or good Upper Second Class degree result (references will be required)
  • In the middle years of your degree e.g. your visit will take place in the Summer vacation before the start of the final year of study
  • Registered at a UK university for the majority of your degree (for most funding bodies)

Working hours and stipend

Working hours will be 35 hours per week for between 6-8 weeks.

You can expect to receive a stipend of between £180 and 200 per week during your stay if the application for funding is successful. There are also opportunities for unpaid research lab experience.

How to apply

Potential applicants should contact chosen project supervisors by the end of January 2020 at the latest or by the date specified for specific projects below. When contacting supervisors please forward:

  • A copy of your current CV
  • A brief statement of support outlining your interest in the project and your suitability
  • The name of an academic referee

Endogenous mechanisms of drug-efflux and biofilm-formation in Mycobacterium tuberculosis
Professor Sanjib Bhakta – s.bhakta@bbk.ac.uk

The rise of antimicrobial resistance is leading to ever-more untreatable illness. Intracellularly surviving bacterial pathogens have endogenous machinery to evade host defence as well as antibiotic treatment. Drug efflux and formation of biofilms are the two key fundamental mechanisms of intrinsic resistance which renders many antibiotics ineffective against them. Mycobacterium tuberculosis has unique multi-drug transporter protein complexes that allow the pathogen to take up nutrients for survival while allowing it to extrude deleterious ones so as the signalling molecules for quorum-sensing leading to biofilm formation. Aim of this project is to understand the molecular mechanisms of these mechanisms to inform new drug-design as well as repurposing existing drugs (such as NSAIDs) with the aim of reversing the phenotype from tolerant to susceptible thereby developing a novel host-directed adjunct chemotherapy. This interdisciplinary research project will offer the candidate training in structural molecular biology, biochemistry and microbiology research, providing experience of drug discovery and development.

Key References:

Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs.
Maitra A, Bates S, Shaik M, Evangelopoulos D, Abubakar I, McHugh TD, Lipman M, Bhakta S.
Br Med Bull. (2016) 118(1):138-48. doi: 10.1093/bmb/ldw019.

Repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis. 
Maitra A, Bates S, Kolvekar T, Devarajan PV, Guzman JD, Bhakta S.
Int J Infect Dis. (2015) 32:50-5. doi: 10.1016/j.ijid.2014.12.031.

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HTSPOTi whole-cell phenotypic assay.
Guzman JD, Evangelopoulos D, Gupta A, Birchall K, Mwaigwisya S, Saxty B, McHugh TD, Gibbons S, Malkinson J, Bhakta S.
BMJ Open. (2013) 20;3(6). pii: e002672. doi: 10.1136/bmjopen-2013-002672.

Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials.
Gold B, Pingle M, Brickner SJ, Shah N, Roberts J, Rundell M, Bracken WC, Warrier T, Somersan S, Venugopal A, Darby C, Jiang X, Warren JD, Fernandez J, Ouerfelli O, Nuermberger EL, Cunningham-Bussel A, Rath P, Chidawanyika T, Deng H, Realubit R, Glickman JF, Nathan CF.
Proc Natl Acad Sci U S A (2013) 2;109(40):16004-11. doi: 10.1073/pnas.1214188109


Single-molecule biochemistry of CpG islands
Dr. Graeme King – g.king@ucl.ac.uk

Gene expression is initiated at regulatory regions of the genome such as promoters. Many promoters consist of CpG islands, which contain a high density of adjacent cytosine and guanine bases (CpGs). A number of ‘CxxC-domain’ proteins have recently been discovered to exist in humans that specifically recognise CpG islands and help to promote gene expression. This project aims to unravel the molecular pathways through which a key CxxC-domain protein (KDM2A) interacts with CpG islands. To this end, DNA containing CpG islands will be engineered. These substrates will then be studied using a cutting-edge optical tweezers assay to manipulate individual molecules of DNA. By comparing how these substrates respond to mechanical strain in the absence and presence of KDM2A, this project will reveal how KDM2A physically interacts with DNA. In order to establish the sequence-specificity of these interactions, the above experiments will be performed for DNA containing both a high and low density of CpGs islands. Together, the findings from this project will help to understand how CxxC-domain proteins recognise CpG islands and, ultimately, facilitate transcription.


Dissecting molecular mechanisms of microtubule regulation by the neuronal protein doublecortin
Professor Carolyn Moores – c.moores@mail.cryst.bbk.ac.uk

Microtubules are key components of the cytoskeleton and are vital for many aspects of cell function, including cellular organisation, cell division and movement. Doublecortin (DCX) is a neuronal microtubule-associated protein that is essential for brain development, and disruption of its function causes intractable epilepsy. DCX is built from flexibly linked DC domains – NDC and CDC – which mediate microtubule nucleation and stabilisation, but the contributions of each domain to DCX functions are less clear. Research in our group has found that although coupled, each DC domain has a distinct role in microtubule nucleation and stabilisation: CDC is a conformationally plastic tubulin binding module that facilitates microtubule nucleation by binding tubulin oligomers and stabilising tubulin-tubulin contacts in the nascent microtubule, while NDC appears to be provide longer-term microtubule stabilisation.

The overall aim of this project is to engineer the DCX protein to create chimeras that can test our hypothesis about the roles of each DC domain in microtubule nucleation and stabilisation. These protein chimeras will be cloned for recombinant expression in E. coli. If successful, protein purification and biochemical characterisation will be performed to measure microtubule nucleation and stabilisation.

Reference
Microtubule structure by cryo-EM: snapshots of dynamic instability.
Manka SW, Moores CA.
Essays Biochem. (2018) Dec 7;62(6):737-751. PMID: 30315096


Isoform-specific tuning of actin nucleation promoting activity in the Arp2/3 complex
Professor Carolyn Moores – c.moores@mail.cryst.bbk.ac.uk

The Arp2/3 complex is evolutionarily conserved and it plays an essential role in many cellular processes, most notably cell migration, and also has newly identified roles in DNA repair. When activated by nucleation promoting factors, the Arp2/3 complex is unique in its ability to assemble branched actin networks by stimulating new filament growth from the side of existing actin filaments. Because three of its seven subunits exist as two different isoforms, mammals produce a family of Arp2/3 complexes with different properties that may be suited to different physiological contexts. Furthermore, tissue-specific expression patterns of subunit isoforms, together with isoform-specific susceptibility to disease-causing point mutations, point to distinct roles for particular Arp2/3 isoforms. Research in our group have suggested that differences in the ARPC5/ARPC5L subunits provide an explanation for the differences in activities between different Arp2/3 isoform-containing complexes.

The overall aim of this project is to characterise the ARPC5 and ARPC5L proteins to test our hypothesis about the distinct roles of these isoforms in actin nucleation. These protein chimeras will be recombinantly expressed in E. coli and purified, and biophysical and biochemical characterisation of their properties will be performed.

Reference
The Arp2/3 regulatory system and its deregulation in cancer.
Molinie N, Gautreau A.
Physiol Rev. (2018) Jan 1;98(1):215-238. PMID: 29212790


Interactions of complement factor H with its ligands
Professor Stephen Perkins – s.perkins@ucl.ac.uk

The project will address the molecular role of defective plasma proteins in causing disease. Eg: age-related macular degeneration (AMD) is the main cause of blindness in the Western World in the elderly. Deposition of proteins and lipids as “drusen” between the blood circulation and the retina is a major risk factor in AMD. Drusen usually grow in size and spread with age, disrupting the normal function of the retina, but may disappear. We are presently unravelling the many interactions of complement factor H with its ligands and how these may be a crucial factor in causing AMD. In order to clarify the involvement of intact complement factor H with its ligands, the summer project will involve the purification of the homozygous high-risk and low-risk forms of factor H from patient plasma, or their recombinant fragments, then interaction measurements of the two forms with ligands will be made using surface plasmon resonance and/or analytical ultracentrifugation. Alternatively, to follow our mutations web-site (http://www.complement-db.org/home.php), disease-risk mutations in recombinant Factor H fragments will be created by mutagenesis and studied using the same methods to show whether these are causative of disease. Alternatively, the web-site can be edited and updated as a separate project.

References
A revised mechanism for the activation of complement C3 to C3b: a molecular explanation of a disease-associated polymorphism.
Rodriguez E, Nan R, Li K, Gor J & Perkins SJ.
J. Biol. Chem. (2015) 290, 2334-2350. Pubmed 25488663

Additional Requirements

If based at UCL, ideally applicants would have taken BIOC2004 (Protein Structure and Function) and/or IMMU2001 (Immunology), and should provide a UCL PORTICO printout (or transcript) when applying.

Project-specific deadline (for students to make contact) – Monday 13th January 2020.