Alison Inglis, PNAC
I started my PhD with Dr. Roger Williams in October 2014. I first came to the LMB as a summer student in Roger’s lab in 2013. This was a great way of getting some experience of lab work during my undergraduate degree, and an opportunity to see how I fit into the lab and the LMB in general. I really enjoyed my three months here, and it culminated in my return a year later to start my PhD with Roger. My project is based on trying to understand the molecular mechanisms behind cellular stress responses, from both a biochemical and a structural perspective.
For me, the best thing about the LMB is the collaborative ethos that surrounds the lab. I feel very lucky to be part of an institution with so many people willing to invest both time and effort into helping me achieve my goals. A large part of my work so far has been using electron microscopy and being able to work in such an atmosphere, surrounded by both state-of-the-art facilities and world-class expertise, is an incredible opportunity. During the first year of my PhD I had extensive training on the microscopes and this has allowed me to use the instruments freely and independently, with the comfort of knowing that a plethora of experts are just a short walk away. The freedom to pursue my own ideas whilst being surrounded by people who are happy to offer interesting insights into my research is what makes the LMB such a great place to do a PhD. (Alison completed her PhD in May 2018 and is joining ex-LMB PhD student and group leader at Caltech Rebecca Voorhees to do a Postdoc.).
Bunney T. D., Inglis A. J., Sanfelice D. et al.  Disease variants of FGFR3 reveal molecular basis for the recognition and additional roles for Cdc37 in Hsp90 chaperone system
Structure 26(3):446-458.e8. 6 March 2018 DOI: 10.1016/j.str.2018.01.016 PMID: 29478821
Bohnacker T., Prota A. E., Beaufils F., Burke J. E., Melone A., Inglis A. J. et al.  Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention
Nature Communications 8:14683. 9 March 2017 DOI: 10.1038/ncomms14683 PMID: 28276440
Burke J. E., Inglis A. J., Perisic O., et al.  Structures of PI4KIIIβcomplexes show simultaneous recruitment of Rab11 and its effectors
Science 344(6187):1035-1038. 30 May 2014 DOI: 10.1126/science.1253397 PMID: 24876499
Mohammad Mofatteh, Cell Biology
I graduated with a First Class Honours degree in Biomedical Science from King’s College London in 2014. Then I accepted an LMB Cambridge Scholarship for international students and started my PhD at the LMB to embark on my dream journey of becoming a world-class scientist. My PhD project focuses on understanding biological processes involved in transportation and localization of messenger RNAs in the nervous system using Drosophila melanogaster as a model organism. Although localization of mRNAs by active transportation is a well established field, there has been little insight into the detailed molecular mechanism by which mRNAs are transported from the nucleus to their destination before being translated to their corresponding proteins. In my PhD I aim to tackle this challenging and long-term problem by using various genetics, molecular, microscopy and biochemical techniques.
We are supported by world class scientists and excellent scientific facilities at the LMB which help us to receive hands-on training to reinforce our existing skills and acquire new knowledge. We have a very diverse range of resources available in the building including light microscopy, electron microscopy, flow cytometry, crystallisation, NMR, mass spectrometry, scientific computing and workshops. Being at the LMB enables us to explore a biological problem in depth and address our question of interest from different aspects. Another valuable experience that I have gained during my time at the LMB was attending various seminars from different divisions. There are four scientific divisions at the LMB: Cell Biology, Neurobiology, Protein and Nucleic Acid Chemistry, and Structural Studies. This is a real added value to the LMB that people have the opportunity to discuss and learn firsthand from scientists that come from different backgrounds, and therefore can have a totally novel approach to address a biological question. Additionally, there are tremendous opportunities for initiating exciting collaborative projects within different divisions thanks to the very friendly atmosphere present here.
Students are well supported at the LMB and receive supervision from three different project supervisors: two from the LMB and another one from one of the departments within the University of Cambridge. Furthermore, graduate students at the LMB are a member of a college within the University of Cambridge. Being affiliated to a college, we have access to all the facilities and support provided by our college. In addition, divisional offices and the postgraduate student office are very helpful during the entire course. I would recommend the LMB PhD programme to any student who seeks a stimulating environment to do pioneering cutting edge science.
After completing my PhD, I would like to dedicate the rest of my life to science and gain more scientific experience to establish my own research laboratory. I believe that at the end of my PhD at the LMB, I would have gained the knowledge, expertise and most importantly the mindset I require to get closer to my goal. (Mo obtained his PhD in May 2018 and started a Postdoc in Oxford in Jordan Raff’s group working on centrioles).
Mofatteh M. & Bullock S. L.  SnapShot: Subcellular mRNA Localization
Cell 169(1):178-178.e1. 23 March 2017 DOI: 10.1016/j.cell.2017.03.004 PMID: 28340345
Annette Strege, Structural Studies
I started my PhD at the LMB on an MRC-funded studentship in 2014. The aim of my project is to determine the crystal structure of a human G Protein-Coupled Receptor (GPCR). GPCRs are the largest family of membrane proteins in humans. They are very desirable drug targets, with estimates stating that 30 – 50 % of all FDA-approved pharmaceutical drugs specifically target GPCRs, treating a broad range of conditions including allergies, pain, high blood pressure and depression. Obtaining new structures of human GPCRs, and understanding how different compounds bind to them, is important for structure-based drug discovery.
I feel very privileged to have the opportunity to work on such a challenging project in such an exceptional institution. Crystallising a GPCR is not easy, in fact there are only around 30 unique GPCR structures published to date, despite the fact that there are hundreds encoded by the human genome. This is not for lack of trying, but simply because GPCRs are extremely small, hydrophobic and flexible, making them inherently difficult to crystallise. Much time, money, and some luck is needed to obtain their crystal structures.
The network of support in the LMB is outstanding. In addition to the amazing scientific facilities, all staff and students have access to a wide range of in-house support facilities, including a media kitchen, instrument services, a mechanical workshop, and IT – and all of these will usually help you straight away (this includes making hundreds of litres of media for you, fixing broken centrifuges or computers, or building and even 3D-printing anything you might need for your research!). In addition, I work alongside lots of incredibly smart and experienced scientists from diverse backgrounds, who always have useful insights into anything I discuss with them. This combination of great facilities, great expertise, and a generally friendly and collaborative environment has already helped me learn a lot and make lots of progress during the first half of my PhD. I’m looking forward to learning and discovering more during the rest of my time at the LMB. (Annette completed her PhD in May 2018 and is currently taking a career break before considering options in biopharma or in areas unrelated to her PhD).
Nehmé R., Carpenter B., Singhal A., Strege A., et al. .
Mini-G proteins: Novel tools for studying GPCRs in their active conformation
PloS one 12(4):e0175642. 20 April 2017 DOI: 10.1371/journal.pone.0175642 PMID: 28426733
Strege, A., Carpenter, B., Edwards, P. C. & Tate, C. G .
Strategy for the thermostabilization of an agonist-bound GPCR coupled to a G Protein
Methods in Enzymology 594, 243-264, DOI:10.1016/bs.mie.2017.05.014
Magnani F., Serrano-Vega M. J., Shibata Y., Abdul-Hussein S., Lebon G., Miller-Gallacher J., Singhal A., Strege A., Thomas J. A., Tate C. G.  A mutagenesis and screening strategy to generate optimally thermostabilized membrane proteins for structural studies
Nature Protocols 11(8):1554-1571. August 2016 DOI: 10.1038/nprot.2016.088 PMID: 27466713
Jake Watson, Neurobiology
My PhD research is focused on gaining a molecular understanding of the basic unit of cell communication in the brain: the synapse. This connection is highly dynamic and changes that occur at this level are the fundamental basis of learning and memory for an organism as a whole.
I use electrophysiological measurements, to record the synaptic currents of connected neurons, which can be modulated using transgenic mice or exogenous gene expression. The functional changes that occur can be understood further using super-resolution microscopy techniques that I have learnt during my PhD.
The LMB is an exceptional place for PhD research, as here, not only is the research focused on answering the most significant questions in a field, but no expense is spared in allowing cutting-edge research to be done. I have found it particularly useful that, because of the diversity of research going on here, any new approach that I would like to utilise can be learnt from an expert already using it within the building. With specialised teams and equipment for techniques such as light-microscopy and flow-cytometry and a workshop for invention of new experimental apparatus, a multi-disciplinary approach to studying a biological system could not be easier to achieve. Being on the doorstep of Cambridge University, means that students are immersed in an environment with scientists who can offer a wealth of new ideas and perspectives, which has given me invaluable experience. This collaborative expertise and research focused attitude are what makes the LMB a world-leading research institution and a unique place to pursue scientific training. (Jake submitted his thesis in March 2018 and will continue his work with a short postdoc in the Greger Lab).
Davies B., et al.  A point mutation in the ion conduction pore of AMPA receptor GRIA3 causes dramatically perturbed sleep patterns as well as intellectual disability
Human Molecular Genetics 26(20):3869-3882. 15 October 2017 DOI: 10.1093/hmg/ddx270 PMID: 29016847
Greger I. H., Watson J. F., Cull-Candy S. G.  Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
Neuron 94(4):713-730. 17 May 2017 DOI: 10.1016/j.neuron.2017.04.009 PMID: 28521126
Watson J. F. Ho H., Greger I. H.  Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain
ELife 6: e23024. 14 March 2017 DOI: 10.7554/eLife.23024 PMID: 28290985
García-Nafría J., Herguedas B., Watson J. F., Greger I. H.  The dynamic AMPA receptor extracellular region: A platform for synaptic protein interactions
Journal of Physiology 594(19):5449-5458. 1 October 2016 DOI: 10.1113/JP271844 PMID: 26891027
García-Nafría J., Watson J. F., Greger I. H.  IVA cloning: A single-tube universal cloning system exploiting bacterial In Vivo Assembly
Scientific Reports 6:27459. 6 June 2016 DOI: 10.1038/srep27459 PMID: 27264908