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 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. For summer 2022, we anticipate that in-person lab work will be possible. Please explore the projects below.

Eligibility

Opportunities are funded by a number of learned societies. Please check the application deadlines and eligibility criteria for the specific schemes. In order to be eligible for a research bursary from these organisations you must usually 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 Thursday 31 March 2022.
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


Project supervisor/ host lab: Prof Ivan Gout

Email: i.gout@ucl.ac.uk

Website: https://www.ucl.ac.uk/biosciences/people/gout-ivan

Project: Exploring the antioxidant function of coenzyme A and the Warburg effect in cancer

Otto Warburg noticed an abnormal dependence of cancer cells on glycolysis as the sole source of ATP production, even in the presence of oxygen. The presence of oxygen allows normal cells to complete both steps of respiration: glycolysis and oxidative phosphorylation. Therefore, cancer cells are wasteful as they use a lot more glucose to produce enough energy for growth and survival. Being dependent on glycolysis cancer cells also gain some advantages.
Coenzyme A is an essential component of the oxidative phosphorylation pathway. It is used to generate metabolically active CoA thioesters (Acetyl-CoA, Succinyl-CoA), which drive the Krebs cycle. We have recently discovered that CoA functions as a major cellular antioxidant under oxidative or metabolic stress via a novel PTM termed protein CoAlation. To date, more than 2100 proteins were found to be CoAlated in eukaryotic and prokaryotic cells. A significant increase in protein CoAlation was found in pathologies associated with oxidative stress, including neurodegeneration and cancer.
Extensive protein CoAlation was observed in hepatocellular carcinoma (HCC). This project is aimed at preparing samples, mass spectrometry analysis (MS) and bioinformatic analysis of CoAlated proteins from HCC (in collaboration with the MS group at the Crick Institute).


Project supervisor/ host lab: Dr Brian Ho

Email: brian.ho@bbk.ac.uk

Website: www.brianholab.com

Project: Suppression of type 6 secretion system activity by a conjugative plasmid

The type 6 secretion system (T6SS) is a bacterial nanomachine used by several different Gram-negative species to deliver toxic proteins into adjacent cells. Delivery of these toxic proteins allows the bacteria to kill off both bacterial and eukaryotic competitors. In the lab, T6SS activity can be assayed by detecting the secreted protein substrates (Hcp), by measuring bacterial killing, or through fluorescence microscopy.
Previously, we have observed that some bacteria species (Pseudomonas aeruginosa and Acinetobacter baylyi) that normally express a T6SS have this T6SS activity suppressed when they acquire the broad host-range conjugative plasmid RP4. As shown in the figure below, when ADP1 acquires the RP4 plasmid, it no longer secretes Hcp (a T6SS secretion substrate) and is no longer able to kill E. coli bacteria grown in competition. In P. aeruginosa, fluorescent foci indicating T6SS structure assembly and activity are eliminating once RP4 is introduced.
The goal of this project will be to determine what aspect of this plasmid is responsible for the loss of T6SS activity. Specifically, we will (1) use qPCR and western blotting to determine if there is gene silencing or post-translational regulation and (2) use genetic knockout screening and gene cloning to identify critical genes on the plasmid responsible for the T6SS suppression.

Related publications
Basler M, Ho BT, Mekalanos JJ. Cell. 2013 Feb 14;152(4):884-94.
Ho BT, Basler M, Mekalanos JJ. Science. 2013 Oct 11;342(6155):250-3.
Kolatka K, Kubik S, Rajewska M, Konieczny I. Plasmid. 2010 Nov;64(3):119-34.


Project supervisor/ host lab: Prof Stephen Perkins

Email: s.perkins@ucl.ac.uk

Website: https://www.ucl.ac.uk/biosciences/departments/smb/perkins

Project: Interactive databases for genetic variants in the coagulation proteins

The project will address the molecular role of defective plasma proteins in causing disease. We have generated well-received interactive databases that combine genetic variants in specific plasma proteins with disorders such as in haemophilia or in inflammatory disease caused by variants in the complement proteins (see our variants web-sites http://www.factorxi.org/ and http://www.complement-db.org/home.php). The databases are useful for both clinicians and basic science researchers. Genetic variants in the evolutionarily-related coagulation proteins of haemophilia (excessive bleeding and failure to clot) are involved in Haemophilia A and B, as well as a number of rare types of these disorders. There, we have created databases for the F7, F8, F9, F10 and F11 genes [Ref 1], several of which are being updated at present. The aim of this summer project is to upgrade and update one of our coagulation databases to bring it up-to-date during the 8 weeks of the studentship. The student will perform literature searches and searches of other on-line resources, assemble these in a MySQL database, learn web-site programming, and present the web site on-line. These are transferable skills that are useful in many contexts. As a computational project, this project is relatively unaffected by COVID, and can be done on-campus or off-campus.

Requirements

If based at UCL, ideally taking BIOC2004 (Protein Structure and Function) and/or IMMU2001 (Immunology). Please provide a brief CV, a supporting statement of why you are interested in the project, the name of an academic referee, and your UCL PORTICO printout (or transcript) when applying.

Deadline (for students to make contact): 

One paid summer internship should be available for 8 weeks. Applications by Monday 14th February 2022.

References

  1. Harris, V.A., Lin W. & and Perkins, S. J. (2021) Analysis of 272 genetic variants in the upgraded interactive FXI web database reveals new insights into FXI deficiency. Thromb. Haemost. Open. In press. https://doi.org/10.1055/a-1683-8605.
  2. Osborne, A. J., Breno, M., Borsa, N. G., Bu, F., Fremeaux-Bacchi, V., Gale, D. P., van den Heuvel, L. P., Kavanagh, D., Noris, M., Pinto, S., Rallapalli, P. M., Remuzzi, G., Rodriguez de Cordoba, S., Ruiz, A., Smith, R. J. H., Vieira-Martins, P., Volokhina, E., Wilson, V., Goodship, T. H. J. & Perkins, S. J. (2018) Statistical validation of rare complement variants provides insights on the molecular basis of atypical haemolytic uraemic syndrome and C3 glomerulopathy. J. Immunology. 200, 2464-2478. Pubmed 29500241 DOI: https://doi.org/10.4049/jimmunol.1701695.

Project supervisor/ host lab: Dr Anthony Roberts

Email: a.roberts@mail.cryst.bbk.ac.uk

Website: www.roberts-lab.com

Project: Building the cilium with ATP-driven molecular motors

The goal of this project is to elucidate the mechanisms underlying cilium construction, in particular the role of the ATP-driven transport complexes. Virtually every cell type in the human body builds a cilium: a microtubule-based projection from the plasma membrane. It has emerged that these antennae-like structures are crucial for sensing light, smell, fluid flow, and morphogens. Their dysfunction is associated with a variety of human disorders, including obesity, blindess, kidney disease, and developmental defects.

How the cell builds the cilium – a complex organelle with defined size, architecture, and protein composition – is a major unsolved question. Central to cilium construction are the molecular motors kinesin and dynein. These motor proteins transport building blocks and signaling molecules to and from the cilium tip, using ATP hydrolysis to move along ciliary microtubules.

Elucidating the structure and mechanism of the ciliary motor protein complexes has been challenging, in part because they are formed by large subunits that fail to fold correctly when expressed in bacteria. In this project you will exploit eukaryotic protein expression systems [1] to produce and analyze protein constructs and thereby investigate how the motors move and are regulated. In addition to molecular biology and biochemistry, you will gain exposure to cryo electron microscopy and single-molecule fluorescence microscopy, providing insight into the structure and dynamics of this molecular machinery.


Building the cilium with ATP-driven molecular motors. (A) Depiction of the cilium, its microtubule doublets and IFT trains propelled by kinesin and dynein. (B) The cryo-EM structure of the 1.4 MDa dynein-2 complex, recently solved in the group1, which raises a number of mechanistic questions.

 

References

  1. Toropova K, Zalyte R, Mukhopadhyay AG, Mladenov M, Carter AP, Roberts AJ. (2019) Structure of the dynein-2 complex and its assembly with intraflagellar transport trains. Nature Structural & Molecular Biology 26(9):823-829.