Brief profiles of two MRC-funded Doctoral Training Programme students

       

Evgenia Markova and Laura Pokorny are PhD students who joined the UCL-Birkbeck MRC funded Doctoral Training Programme in Autumn 2016. PhD students on this programme complete rotation projects in year 1 before choosing and developing their PhD project. Both Evgenia and Laura are looking forward to increasing opportunities to engage with new intakes of students.

This post is part of a series about Doctoral Training Programmes which offer funded PhD studentships at Birkbeck. Many thanks to Laura and Evgenia for taking part.

Evgenia Markova

I obtained a BSc in Genetics from the University of York and during the course of my degree I completed summer internships in the Bulgarian Academy of Sciences and in Genika, a genetic medico-diagnostic laboratory. It was at this point that I started considering a career in science, as I was surrounded by experts in their respective fields who warmly welcomed me into their research environment. I also completed a year-long placement in a biotechnology company, Heptares Therapeutics, where I discovered a passion for biochemistry and structural biology, which ultimately determined my choice of a PhD topic.

Rotation Projects (Year 1)

‘My choice of PhD project emerged through engagement with rotation projects which took my research in novel directions. This flexibility to develop and mould the final project has been a great opportunity.’

Rotation 1: My first rotation project ‘Structural elucidation of a component of the COPII secretion system’ was with Dr. Giulia Zanetti (ISMB, Birkbeck) where I encountered electron microscopy for the first time and obtained preliminary structural information on a component of the COPII secretion system.

Rotation 2: My second rotation ‘Age-dependent neuroinflammation in the brain of a Wnt signaling pathway mutant’ was with Dr. Patricia Salinas at the MRC LMCB and utilised immunofluorescence to study the time-dependent brain inflammation profile of a Wnt signalling pathway-defective mouse model.

Rotation 3: Finally, I spent my third rotation ‘Single-molecule fluorescence investigation of the COPII coat assembly’ in Dr. Alan Lowe’s lab in (ISMB, Birkbeck) where I studied the dynamics of an endoplasmic reticulum membrane model as remodelled by purified COPII proteins.

‘The ISMB has excellent facilities which provide access to structural biology and cryo-EM. It has been easy to move between facilities at Birkbeck and UCL as part of the jointly run ISMB.’

PhD Project: The Kinetics and Assembly of the COPII Secretion System (Year 2 onwards)

The intracellular trafficking of biomolecules is an essential property of eukaryotic systems. The COPII vesicular transport system is responsible for anterograde intracellular transport processes at the ER membrane, where COPII component-lined vesicles incorporate protein and lipid cargoes. My project aims to investigate the mechanisms of COPII budding and coat assembly, which are currently poorly characterised. I will study COPII assembly and dissociation using an established membrane model,

Giant Unilamellar Vesicles
Giant Unilamellar Vesicles, a common membrane model, as visualised through the incorporation of a fluorescent lipid into the mixture used for their formation.

Giant Unilamellar Vesicles (GUVs), and the mammalian COPII proteins, as expressed and purified from insect cell culture. I will utilise cryo-electron microscopy and single-molecule fluorescence in the study of the COPII coat assembly through in vitro reconstitution. My PhD supervisor is Dr Giulia Zanetti, ISMB, Birkbeck.

Laura Pokorny

I studied for an undergraduate degree in Biochemistry at the University of York. In the summer between my second and third year I carried out a 2 month research placement in Paul Pryor’s lab at the Centre for Immunology and Infection at the University of York, where I was identifying chlamydial effector proteins involved in disrupting the trafficking of the bacterium to the host lysosome. I really loved working in a research setting and this was when I realised I wanted to do a PhD and pursue a career in research.

Rotation projects (Year 1)

Rotation 1: My first rotation ‘Manipulation of Nuclear Function by Chlamydia trachomatis’ was in Dr Richard Hayward’s lab (ISMB, Birkbeck). Previous research in the Hayward lab had identified alterations in nuclear architecture during infection by C. trachomatis. Namely, the nuclear shape becomes distorted in infected cells, lamin A/C is decreased at the inclusion distal face of the nucleus, and there was a degradation of nucleoporins at the inclusion proximal face of the nucleus. I confirmed these findings by aiming to understand the mechanism underlying the lamin A/C decrease.

Chlamydial inclusions (green) and lamin A/C on the nucleus (red) of inclusions which are 48 hours post infection.

Caspase 6 is a candidate for the degredation of lamin A/C due to the fact that lamin A/C is degraded by caspase 6 during apoptosis. By treating infected cells with a drug which inhibits caspase 6, I was able to block the lamin A/C decrease in infected cells. This was shown by confocal microscopy and by western blot.

 

Rotation 2: My second rotation ‘A novel mechanism of targeting and transport of a P. falciparum protein down the secretory pathway’ was in Dr Andrew Osborne’s lab (ISMB, UCL).  The mechanism leading to protein transport, and in particular trans-membrane protein transport, in P. falciparum is not completely understood. Proteins destined for export must cross many membranes of the parasite before entering the host cell. Models have proposed whereby TM proteins are extracted from membranes at various stages of the secretory pathways and trafficked via chaperones (Papakrivos, Newbold and Lingelbach., 2005; Kneupfer et al., 2005; Gruring et al., 2012). However, the concept of pulling proteins out of membranes during protein export is unsupported outside the Plasmodium field. Recent work in the Osborne lab and others has provided evidence that the PNEP protein Pf332, which has a single TM domain, behaves in line with this extraction model. I used yeast as a model organism and showed that, when Pf332 is expressed in yeast, there is a subset of soluble protein. This suggests that the machinery needed to pull the protein out the membranes is conserved in eukaryotes. In this rotation I used techniques including western blotting, parasite culturing, cloning, and florescence microscopy.

Rotation 3: In my third rotation ‘Single-molecule studies of the molecular mechanisms of the nuclear pore complex during C. trachomatis infection’ in Dr Alan Lowe’s lab (ISMB, UCL) I used super-resolution microscopy to gain images of the nucleoporin degradation seen in my first rotation, and to learn more about the kinetics of importin-beta transport in the nucleus during infection. I used the technique of photoactivated localization microscopy (PALM). In short, PALM imaging uses the principle of stochastically activating, imaging and photobleaching photoswitchable fluorescent proteins in order to temporally separate closely spaced molecules (Betzig et al., 2006). The resolution achieved in PALM imaging is over an order of magnitude higher than the diffraction limit of light. By transfecting infected cells with importin-B (nuclear transport receptor) tagged to a photoswitchable fluorescent protein and imaging by PALM, we could gain a much higher resolution picture of the organisation of the nuclear pores, and could follow the kinetics of transport via single-particle tracking.

‘Working within the ISMB environment has been a great way to find out more about the work of other PhD students and staff through weekly presentations during term time known as Friday Wraps’

PhD project: Studying Vaccinia virus fusion using a minimal model system (Year 2 onwards)

Vaccinia virus (VACV) is the prototypical Poxvirus. Poxviruses enter cells by acid mediated fusion, using the most complicated virus fusion machinery identified. Whilst genetics indicates that poxvirus fusion relies on 12 viral proteins, to date the organisation of this machinery, its mechanism of fusion, its fusion peptide, and the structural and molecular details of poxvirus fusion remain a mystery. Therefore to address this lack in our knowledge, I aim to develop a new minimal model system to study VACV entry and fusion. This system will be amenable to super-resolution imaging studies allowing us an unprecedented view into the biological requirements of viral entry. My PhD supervisor is Dr Jason Mercer LMCB.

Wellcome Trust 4-year Interdisciplinary PhD Programme

Wt logo              ISMB logo

This brief profile of the Wellcome Trust 4 Year PhD Programme in Structural, Computational and Chemical Biology is part of a series looking at Doctoral Training Programmes which offer funded PhD studentships at Birkbeck. Many thanks to Dr Cara Vaughan (Programme Co-Director) for answering the following questions.

How would you describe this Wellcome Trust 4 year PhD programme?

This is a fantastic interdisciplinary program that enables students to experience three distinct yet synergistic fields, that together can lead to the most exciting developments in biomedical research. These are structural, molecular, cellular biology and biophysics, computational biology and chemical biology.

Which departments at Birkbeck are taking part in this PhD programme?

The Department of Biological sciences, part of the Institute of Structural and Molecular Biology (ISMB). The department forms a part of a diverse and interdisciplinary environment across the PhD programme and the ISMB.

What strengths does Birkbeck bring to this Doctoral Training Programme?

Research in the Department of Biological Sciences is world-class, with strengths in structural and computational biology.

 conserved mechanisms of microtubule-stimulated ADP release
The conserved mechanisms of microtubule-stimulated ADP release (Professor Carolyn Moores’s lab)

How is the programme structured?

The first year involves rotation projects in 3 different labs, each specialising in one of the 3 disciplines within the program. In addition, students attend both foundation and advanced lectures to strengthen their understanding in these fields. At the end of their first year students choose the project that will be the focus of the remainder of their PhD and spend the remaining 3 years affiliated with that lab answering exciting questions at the forefront of biomedical research. Further information about the programme structure is available on the WT PhD Programme webpages.

What kinds of resources and facilities are available to students who are offered a place on the programme?

The ISMB is extremely well-equipped with world-class instrumentation and research facilities in all three disciplines.

Anthony Roberts lab image
The dynein–Lis1 interface (Dr Anthony Roberts’s lab)

How are PhD students supported during their postgraduate research and in preparing for their careers after the PhD?

Students are supervised by senior scientists who are recognised at an international level in their chosen field, both during rotations and during the PhD project itself. They are exposed to a highly interdisciplinary environment through which they gain experience of working in a dynamic and challenging way. In addition to opportunities to undertake taught programmes across a range of ISMB disciplines students also take part in WT PhD programme activities including literature clubs, and gain experience in presenting their data. Students can attend career days, where PhD-qualified scientists working in non-academic environments give talks and meet students and they can also access professional development opportunities within Birkbeck and UCL.

What are the advantages for students taking part in this Wellcome Trust PhD programme?

Exposure to and involvement in some of the best biomedical research in the UK and interdisciplinary training which is shaping the future of biomedical research. Profiles of some of our PhD students are available.

Are there any features of supervision within the Wellcome Trust programme that you would like to highlight?

In addition to every student having a thesis committee that meets at regular intervals throughout the 4 years, the student also meets the program director/co-director to ensure that the project is on track, to resolve any issues early on and to ensure that the student has the best possible outcome form their PhD.

Cryo-electron tomogram
Cryo-electron tomograms of a reconstituted COPII budding reaction (Dr Giulia Zanetti’s lab)

How can students find out about potential projects and supervisors at Birkbeck?

A list of potential supervisors and example projects are available on our ISMB WT PhD Programme website.

How would you describe your role within this Wellcome Trust PhD programme?

As co-director I work closely with the director, Finn Werner, and the administrative support staff to ensure the smooth running of the program. This includes everything from sifting through applications to the program, to interviewing students, to a more pastoral role for students in the later years of their PhD.

What background and experience would successful applicants be able to demonstrate if they are interested in joining the programme?

This is a highly competitive program and successful students are exceptional. They should have an excellent degree in one of the disciplines in the program, or a related discipline, and hands on experience of working in a lab in one or two of these areas covered within the program.

What do students need to do to apply?

Students must follow instructions for applicants carefully. Student need to complete an online Graduate Student application form from UCL and submit a single document with a current CV and a statement explaining why they are a suitable candidate. They also need to provide details of 2 referees. Full instructions for applicants are available here.

Are there any key dates to be aware of?

  • The deadline for applications is 5 January 2018
  • The interview dates are 25 and 26 January 2018

Upcoming Birkbeck Wellcome ISSF Deadline (31 October)

Birkbeck has a Wellcome Trust Institutional Strategic Support Fund (ISSF) which provides opportunities for PhD researchers whose work falls under the broad remit of the Wellcome Trust:

  • Biomedical research
  • Medical humanities
  • Medical social sciences

The next deadline for Birkbeck Wellcome Trust ISSF applications is 31 October.

Opportunities for Birkbeck PhD students could include the following:

  • If you are a PhD researcher completing your thesis can apply for funding to enable you to complete publications or develop public engagement or dissemination activities. The funding covers salary costs up to six months beyond the end of your formal period of study (on the starting point of the Researcher 1 pay scale).
  • If you are a current PhD researcher you can apply for funding of up to £5,000 to carry out public engagement or interdisciplinary activities for a period of up to three months. Please note: this period will represent a formal break in your studies, if your PhD funder allows it.

For further information about the ISSF awards and for details of how to apply please view the ISSF website.

A brief profile of the London NERC DTP with Professor Andy Carter

This brief profile of the London Natural Environment Research Council (NERC) DTP is the first in a series of brief profiles looking at Doctoral Training Programmes which offer funded PhD studentships at Birkbeck. Many thanks to Professor Andy Carter for answering the following questions.

How would you describe the London NERC DTP?

The London NERC DTP is a partnership of nine world-leading research organisations across London. The partnership, which includes Birkbeck, is focused on excellence in environmental science research training and delivery of a transformative inter-disciplinary experience for PhD students.

How would you describe your role within this London NERC DTP?

I am a member of the Management Board of the London NERC DTP and postgraduate tutor for the Department of Earth and Planetary Sciences at Birkbeck.

What are the advantages for Birkbeck PhD students taking part in the London NERC DTP?

Unlike most other DTP’s for the first six months students receive core interdisciplinary training as a cohort covering the full spectrum of environmental science. This engenders a strong sense of community and support. Training is given at each of the partner institutions including the Natural History Museum, Kew, UCL, Kings, Queen Mary and the Institute of Zoology. Part of the training requires the student cohort to organise and lead a field trip to California and an annual conference with the DTP’s at Imperial College and Reading University to showcase student work.

Image by Rebecca Parrish

How is the programme structured?

Year 1

In the Autumn term of year 1 students undertake core multi-disciplinary skills training, then in the Spring term they continue with core training and PhD project development. As part of their training students have taken part in a 10-day California Field Training Course. Within the Summer Term students relocate to the institution where they will be carrying out their PhD research.

Year 2

Alongside PhD supervision bespoke training courses are provided to develop specific skills. During their second year students are considered for upgrade from MPhil to full PhD status.

Years 3-4

Students continue research as well as preparing their thesis for submission and viva in year 4.

Student training. Image by Sally Faulkner

What kinds of resources and facilities are available to students who are offered a place on the programme?

Aside from training, each student is allocated a research grant of between £6,000 to £8,000 to cover any expenses associated with their project.

How are PhD students supported during their postgraduate research and in preparing for their careers after the PhD?

Students are able to access a range of training and networking workshops, events and internships: to develop business and entrepreneurial skills, engage with industrial, commercial and policy end-users; and to develop specific skills in collecting, interpreting and commodifying environmental data. These opportunities include “Innovation Week’ a 5-day integrated programme of lectures and workshops at the Siemen’s Crystal building at the Royal Victoria Docks in East London, covering topics at the interface between environmental science, business, and science policy.

What background and experience would successful students be able to demonstrate?/ What do students need to do to apply?

Applicants must meet UK residency criteria and language requirements. Applicants are expected to have a 2:1 or higher in a relevant degree, or equivalent work experience.

How can students find out about potential London NERC DTP projects and supervisors at Birkbeck?

Potential applicants should visit the London NERC DTP website for further information about the programme and about how to apply. Applications for London NERC DTP studentships beginning in Autumn 2018 are expected to open in November 2017 with a deadline for applications expected to be in early January 2018. Potential student projects at Birkbeck will be made available on the Earth and Planetary Sciences website in November 2017 once applications for studentships open.