Queen Mary University of London and the University of Southampton are proud to run a joint Medical Research Council (MRC)-funded Doctoral Training Partnership. Starting in 2016 in collaboration with the MRC, we have established a successful programme that identifies excellent students and matches them with outstanding research projects. The MRC DTP programme began with a 4-year MRC-funded MRes/PhD programme in the areas of translational immunology, inflammation and cancer. Recently we also appointed additional MRC-funded students to study projects addressing skills of national shortage and iCASE studentships who study in association with a commercial partner. Together with university funding, the joint programmes have appointed over 50 students to our MRC DTP to date.
The MRes/PhD is undertaken at either the School of Medicine and Dentistry, Queen Mary or the Faculty of Medicine, University of Southampton. In the MRes year students study (at either Queen Mary or Southampton) three taught modules that include statistics, computational coding and quantitative biology skills. Additionally students undertake three 12-week rotation projects (usually two wet-lab studies and one of which must be predominantly mathematics, computational biology or bioinformatics) which are each assessed by a mini-thesis report. On successful completion and award of the MRes, students select one of the projects as the subject of their 3-year PhD. Thus students experience a variety of research environments and skills that arm them for their future career in the field of science. We are enormously proud of our students, many of whom offer commentary on their experiences to date.
What is your current rotation? I am currently doing a rotation in Stephanie Kermorgant’s lab, investigating whether the cMet signalling pathway, stimulated by HGF, leads to an increase in PDL1 expression.
What skills have you developed so far, and what skills do you hope to develop? I have learnt how to perform western blotting. I think I will go on to develop skills in immunofluorescence and microscopy.
How have you found the mathematic/computational component of the DTP? It's been incredibly valuable to have assigned time to learn how to use R. It's something I think will be incredibly useful in my research career, and I just don’t think I could have invested the time independently to learn it.
What have you enjoyed most and least about your experience so far? I've really enjoyed joining a PhD scheme with three other people. I think the taught computational module has been the most useful. I have least enjoyed the research methods module; it, and its coursework, are quite time consuming.
What rotations have you completed so far? My first rotation was under the supervision of Dr Pradeep Madapura at the Blizard Institute and was titled "Generation of MSL and MOF Knockdown Cell Lines to Study Their Role in Enhancer Function and Gene Regulation." In this project I was trying to produce stable gene knockdown cell lines in which the histone acetyltransferase proteins MSL and MOF could be studied in order to shed light on their role in development and cancer.
I undertook my second rotation in Dr Gunnel Hallden’s lab at Barts Cancer Institute, working on oncolytic adenoviral therapy for the treatment of prostate cancer. The aim of this project was to develop new methods, such as combining with peptides, to enhance the delivery of the therapeutic adenoviruses to the prostate cancer cell and ultimately increase cell killing.
What skills have you developed so far, and what skills do you hope to develop? I have been fortunate to develop a wide range of laboratory skills over the first two rotations. These include a number of fundamental research techniques such as cell culture, PCR, western blotting just to name a few, and I feel that this will stand me in strong stead for work that I will encounter throughout and beyond my PhD. As my third rotation will be in the form of a literature review, I really hope to be able to develop my ability to critically review other research papers.
How have you found the mathematic/computational component of the DTP? One hugely interesting aspect of this course is the taught computational module that is undertaken in Southampton. This was a real eye opener for me as I had previously no experience in this at all and went into the course fairly nervous about it. It was so encouraging that by the end of the module I felt I had a solid foundation understanding of bioinformatics and how it can be applied. I look forward to trying to develop this more during my PhD.
What have you enjoyed most about your experience so far? I think the most enjoyable aspect of the programme is without doubt the opportunity to spend time in different labs doing completely different types of research. Not only do you learn a wide range of different skills and see how different researchers work, but it allows you to make a very informed decision on which project you wish to select for the PhD.
What is your current rotation? The title of my current rotation project is 'Investigating the impact of eradicating cancer cells with amplified centrosomes in cancer.' Centrosome amplification is a hallmark of cancer and has been shown to promote tumorigenesis in vivo, leading to chromosome instability (CIN) and increased invasive capacity of cells. I am currently helping to generate a new cell line to investigate what happens to the tumour microenvironment (TME) when cells with extra centrosomes are removed.
What skills have you developed so far, and what skills do you hope to develop? So far I have developed both my cellular and molecular biology skills through experience with gateway cloning and immunofluorescence staining. I have also become far more confident with microscopy and tissue culture. Moving forward in the project I hope to develop skills in tissue staining and identifying TME components.
What have you enjoyed most and least about your experience so far? I am thoroughly enjoying becoming confident working independently in the lab, developing my own ideas and expanding my current knowledge of the cell cytoskeleton. It has been a challenge to become accustomed to managing my own time and not allowing the work load to become overwhelming.
What is your current rotation? The title of my current rotation project is 'Discovering the role of PARP1 BRCT domain in DNA repair and elucidating the potential of it's inhibition in cancer treatment.' This rotation project with Zuzana Horesji was aimed at the understanding of DNA damage response proteins. We are looking at HRPU and other HRPU homology proteins, in particular their expression levels at the protein level in response to damage, their activity before and after phosphorylation and how this affects function. This is using cloning techniques to produce novel truncation of the protein of interest as well as using cell culture followed by immunoprecipitation to investigate protein interactions.
What skills have you developed so far? So far, skills developed have been predominantly in the laboratory environment, particularly cloning techniques. As well as that, the Southampton computational module has been quite enlightening and I have come out with a working understanding of R coding as well as it uses for 'omics research.
How have you found the mathematic/computational component of the DTP? The bioinformatics component taught at Southampton is structured in a very good way and helps initially with getting to grips with R coding. However after this initial session with R the level of coding increases exponentially. Looking at single cell sequencing, principal component analysis etc is quite difficult to understand. The coursework for this section is quite helpful to get to grips with the techniques.
What have you enjoyed most and least about your experience so far? The most enjoyable aspect of the course for me so far has been learning to use R to a standard which is actually useful. The least enjoyable aspect is balancing lab work with lectures and coursework.
Which rotation did you decide to pursue for your PhD project? I decided to continue with my third rotation for my PhD project, which looked at the role of HER2-CB2 heteromers in the progression of breast cancer. HER2 is an established prognostic marker for invasive breast cancers and HER2 expression in breast cancer can identify patients at risk of progressing to the invasive disease. The cannabinoid receptor 2 (CB2) is closely correlated with HER2 expression in breast cancer patients and administration of Δ9-tetrahydrocannbinol (THC) leads to the senescence of cancer cell growth and an increase in apoptosis. THC was found to cause the dissociation of the HER2-CB2R heteromer and lead to proteasomal degradation of HER2, preventing tumourogenic signalling. In this rotation I developed a 3D model of breast cancer using the breast cell line MCF10A, with inducible expression of HER2 and CB2, to investigate the functional role of these receptors in breast cancer progression. I decided to continue with this rotation for my PhD project due to the importance of 3D models in in vitro biology, the level of collaboration this project involves and the fascinating biology. I will continue to study the role of HER2 and CB2 interaction in breast cancer and how these receptors influence signalling, metabolism and the overall progression of breast cancer.
What skills have you developed so far? The rotation year offered valuable experience developing a wide range of lab skills and the ability to plan and carry out experiments independently. Throughout my PhD I expect to be competent at many techniques in the lab, whilst also developing my data analysis and interpretation, presentation skills and critical analysis of other scientists’ work.
Have you contributed to any publications so far? I currently am a co-author on a paper that is under review.
Have you attended, presented a poster or spoken at any conferences? I attended the Biochemical Society conference: Cell Signaling and Intracellular Trafficking in Cancer Biology: Interplay, Targeting and Therapy in Turin Italy on 21-24 October 2019.
What rotations did you complete during your first year of the programme? I completed the following rotations: Production of a recombinant fragment of human surfactant protein A (SP-A) using a mammalian expression system; Petri net computational modelling of dendritic cell gene regulatory network in response to Plasmodium falciparum; and The cellular origin of microRNA dysregulated in chronic obstructive pulmonary disease (COPD) lung-derived extracellular vesicles (EVs).
What did you choose as your PhD project and why did you choose it? My PhD project investigates the hypothesis that microRNA differentially expressed in COPD lung-derived EVs compared to healthy controls are selectively packaged and released from epithelial cells as a form of intercellular communication mediating chronic inflammation in COPD. I chose this project after being introduced to the field of EVs in my final MRes rotation project with the Pulmonary Immunology Group. Over recent years the role of EVs in disease has become an exciting and quickly evolving area of research with many novel diagnostic and therapeutic applications being investigated. In addition I chose to join the Pulmonary Immunology Group as they offered the knowledge and support required to complete a successful PhD project.
What skills have you developed so far? I have so far developed a wide range of technical and transferable skills relevant to my development as a professional researcher. During the MRes I gained valuable skills in statistical and bioinformatic analyses from the taught modules and rotation projects which are really useful both in terms of my current PhD project and future career. I have also gained experience in a variety of laboratory techniques including tissue culture, recombinant protein synthesis, western blot analyses and quantification of microRNAs using real-time PCR. Furthermore I developed skills including communicating with outreach and critical analyses of research. Over the next few years I wish to develop skills including microscopy and making an impact with my research.
Have you attended, presented a poster or spoken at any conferences? I presented at the IPhD and MRC DTP AwayDay in Southampton (2019) and attended the UK Extracellular Vesicles Forum (2019).
Have you completed any additional training? I have completed the Introductory course to 2D image processing and analysis.
What have you enjoyed about your experience so far? Overall what I have enjoyed so far about the iPhD programme is the support and opportunities available to allow you to identify and pursue an area of research you are passionate about.
Which rotation did you decide to pursue for your PhD project? My PhD project is entitled 'Investigating cell intrinsic metabolism of dendritic cells' and is a continuation of my first rotation. I chose this project for a number of reasons. Firstly, it was the project which I was most passionate about. Also, I felt that this project has a strong potential to be fully translatable, from the basic biology, right through to validation in human tissue and identification of potential drug targets for use in clinics. In my particular case I hope to eventually apply my research in a breast cancer setting. Another reason for selecting this project was my supervisors. Between them, they have strong expertise in the fields of immunology and metabolism, with my primary supervisor also being in charge of the metabolomics core facility at Barts Cancer Institute.
What skills have you developed so far? So far during my rotations I have improved my abilities to communicate my research. I have gained experience in a number of techniques: immunohistochemistry, western blot, immunoprecipitation, primary cell culture, microscopy, flow cytometry, handling RNA sequencing data, qPCR. I have also developed my time management and organisation skills.
What skills do you think you will develop going forward? In the future I will gain technical experience in running samples on an orbi-trap mass spectrometer. I will further improve my analytical and experimental design skills. I will also gain skills in more advanced cell culture techniques, and metabolic profiling of cells. Lastly, I will be handling big data sets and developing my ability to extract useful information from these data sets.
How did you find the mathematics/computational component of the DTP? The bioinformatics component of the DTP was very useful, now I feel like, with a little bit of time, I’d manage to work through most data sets. It also gave me the confidence to proactively seek opportunities to use these skills in my rotation projects, and I hope eventually in my PhD project.
Have you completed any additional training so far? I have completed the Home office licensee training course (PILA-C) for my personal license.
What have you enjoyed most and least about your experience so far? I have enjoyed most the opportunity to choose whatever three rotation projects I would like, and as a result, I now have vastly increased my network of scientists within the School of Medicine and Dentistry. I least enjoyed juggling my first rotation with one day a week in Southampton and the taught component on a Wednesday.
What is your PhD project and how did you choose it? My PhD project is to investigate the functional relationship of macrophages in DCIS progression with a focus on the fate of myoepithelial cells. Using and developing a 3D in vitro model of ductal carcinoma in situ (DCIS). My aim is to assess the behaviour of myoepithelial cells in response to primary macrophages of different phenotypes. Characterising DCIS associated macrophages will form an important part of my project. I chose this project due to its clinical relevance and focus on 3D in vitro modelling.
Which skills have you developed so far? I have developed a great deal of independence both at the bench and away developing and planning ideas. The three short rotation projects have taught me that, while things may not always go to plan, there is always a lesson to take away for next time.
Which skills do you think you will develop going forward? I think I will continue to become more independent in making plans and decisions that will shape my final PhD thesis and understand the commitment that is required to be in academia and lead a research group.
How did you find the mathematics/computational component of the DTP? The mathematics/computations component was a full on introduction to R with real datasets to manipulate and understand. While daunting at first for a complete beginner, it has opened my eyes to the value of computational biology in complementing our traditional research.
What have you enjoyed most and least about your experience so far? What I have enjoyed most is being able to work on three short projects with an opportunity to tailor each in line with my specific interest. I would have enjoyed committing 100% of my time to my lab project rather than coursework etc.
What is your PhD project and how did you choose it? I chose to continue with my second rotation with Professor Trevor Graham as my PhD project, which I'm now carrying out on the early immune and genetic events in Lynch syndrome patients and the progression to colorectal cancer. I decided to choose this project due to learning the most while performing my rotation with this group, as well as having a particular interest in the interactions between genomic alterations and the microenvironment contributing to the initiation of cancer. This group is very diverse, containing computational mathematicians, clinical fellows, immunologists and wet lab researchers which makes it a dynamic and inspirational environment to be in.
Which skills have you developed so far? So far during my MRC studentship I have learnt a lot of computational analysis from scratch, such as coding, statistics and AI image analysis. Along with laboratory techniques such as siRNA, CRISPR, RNA/RNA extraction and microscopy techniques.
Which skills do you think you will develop going forward? I'd like to learn single cell techniques like single cell RNA sequencing and further my computational analysis skills.
How did you find the mathematics/computational component of the DTP? The taught MRC computational module gives a very good grounding in the most common types of analysis carried out and basic R coding, which can then go on to be used and developed within the rotations performed.
Have you contributed to any publications so far? I am currently working on a review.
What have you enjoyed most and least about your experience so far? I really enjoyed my three rotations in first year. I think this is an excellent opportunity to get to know what you like best and least in the laboratory and also experience many different ways of working within a lab, ways Principal Investigators work differently and various fields within cancer and immunology.
What is your PhD project and why did you choose it? My project is 'Investigating the therapeutic potential of aGITR (glucocorticoid-induced TNF receptor-related gene) antibodies.' GITR is a co-stimulatory receptor found on the surface of immune cells. In this project, I am testing the therapeutic efficacy of anti-aGITR antibodies produced by the University of Southampton Antibody and Vaccine group, for immunomodulatory tumour therapy. I chose this project because developing therapeutic antibodies is an exciting topic and the university has many research groups that are experts in this field.
What skills have you developed so far? In the lab, I have developed skills in flow cytometry, tissue culture, Biacore, 3D culture of organoids, DropSeq, western blots, analysis of single cell RNA seq datasets and IHC. Other skills I have developed include thesis writing, presenting and the critical appraisal of research articles. I hope to continue to develop my writing skills, presenting skills and in vivo animal work.
How did you find the mathematics/computational component of the DTP? Both RPB and RPC involved analysis of scRNA seq datasets which I really enjoyed. It was nice to develop these skills as computational methods are becoming more prevalent in scientific research.
How have you found your experience so far? There was a really interesting variety of projects available as part of my rotation year. Because of this, I have been able to develop a variety of different skills. The support and guidance throughout has been excellent. I’m happy with how things are going and enjoying the research I am a part of. The away day in my first year was interesting, I got to see the scope of research being undertaken at both the University of Southampton and Queen Mary University of London.
What is your PhD project and how did you choose it? The diverse and highly complex nature of modern biological research produces a high volume of data. Thus, there is unprecedented need to develop tools and methodologies to explain and rationalise these results. The aim of my PhD project is to develop novel logic-based algorithms that overcome the limitations of existing tools used for analysis. Ultimately, the most challenging aspect of this work will be to develop an automated hypotheses generation and validation algorithm. This will be able to employ abductive reasoning in combination with scientific knowledge and expertise to logically analyse not only datasets which suffer from the issues mentioned above but others as well. The resulting hypotheses can then be validated entirely in silico based on information garnered from other databases. If this yields interesting and novel results these can ultimately be tested by carrying out the relevant physical experiments manually.
What skills have you developed so far? I have expanded my skills on general computer-based analysis. Namely, following various courses I have attended at Queen Mary, I have gained more advanced skills in Python-based data analysis. As the main focus of my project is applying a novel approach via logic programming, I have gained a substantial working background, which I am continuously expanding, on the use and application of the LP language Prolog, specifically its SWI-Prolog implementation.
Have you attended, presented a poster or spoken at any conferences? I attended two conferences in 2019. The first was the American Society for Mass Spectrometry (ASMS) conference in Atlanta, Georgia. Here I presented a poster detailing the initial stages of my work relating to explaining the phosphoproteomics dataset I am working on. The second conference I attended was the International Conference on Logic Programming (ICLP) at Las Cruces, New Mexico. As part of the conference I attended a 2-day intense course titled 'Autumn School on Logic Programming' as well as a 1-day workshop on Probabilistic Logic Programming. Through these, apart from a plethora of ideas to pursue as part of my own work, I made a number of connections with potential collaborators.
Have you completed any additional training? I have been accepted as part of the PhD Enrichment scheme at the Alan Turing Institute. For this I will be based at the Institute for six months beginning January of 2020. Here, I will have the chance to collaborate with the researchers within the Institute as well as the various Fellows that are part of it but based elsewhere.
About me: I received my BSc Biomedical Sciences degree from the University of Southampton where I first became interested in Cancer Immunology. This led me to complete an MRes in Cancer Biology at Imperial College London, where I worked in Ovarian Cancer Research and Glioblastoma Research labs. I then joined this MRC DTP at Barts and the London School of Medicine and Dentistry.
Have you attended, presented a poster or spoken at any conferences? I gave an oral presentation at Termis-EU 3D Bioprinting in Cancer Research (2019). I also gave an oral presentation at the International 3D Bioprinting Research Symposium (2019), where I was winner of the young investigator’s oral presentation competition. I gave a poster presentation at BioMedEng (2019).
What have you enjoyed the most and the least about your experience so far? I have mostly enjoyed learning a whole new area of research – bioinformatics. It has been very challenging, but it has been great to be able to use it in real research. It is hard to keep up with the workload as it is a very fast-paced programme, but it has been a new challenge and an enjoyable experience.
What is your PhD project? My PhD project investigates the characterisation of LILRB3, a novel myeloid inhibitory receptor and the generation of a CAR T-cell immunotherapy against this receptor to treat acute myeloid leukaemia.
What skills have you learnt so far? Since my project involves two separate aspects, I have gained a broad range of skills to date. I have had an intense training on molecular biology as a requirement to develop the therapy. I have also gained a variety of in vitro skills ranging from transcriptional assays to co-culture of mouse and human primary cells as well as a range of cell lines. I have also gained in vivo experience including tumour mouse models where I gained various competences to be able to handle mice for experimental studies. As part of the induction statistical course I have gained knowledge and practical skills on how to apply the appropriate statistical tests to support my biological findings.
Apart from my experimental skills, I have also gained other skills such as organisational skills, time management, writing skills, presenting skills and working as part of a team and independently. I also anticipate learning how to fully generate the therapy using viral vectors as well killing assays to enable the therapeutic efficacy of the therapy to be assessed.
Have you attended, presented a poster or spoken at any conferences? Throughout my PhD studies I have attended the following conferences: British Society of Immunology Congress 2019, Liverpool, UK; Cancer Science Unit Conference, Southampton 2018 & 2019; Humanised Mouse Symposium at Cambridge University, UK 2018 & 2019; The Institute for Cancer Vaccines and Immunotherapy Conference at the Royal Society in London, UK.
I presented a poster and received first prize for my poster presentation for two consecutive years at the Cancer Science Unit Conference, Southampton 2018 & 2019. In order to attend the BSI congress 2019 in Liverpool I received a BSI bursary to cover most of the expenses.
Have you completed any additional training? I have gained additional training on structural biology by using a Small-angle X-ray scattering beamline at the European Synchrotron Radiation Facility in Grenoble, France.
About me: My first degree was a BSc in Anatomical Sciences with Industrial Experience, which I completed at the University of Manchester. I went on to obtain an MSc in Cancer and Molecular and Cellular Biology at Queen Mary University of London.
What is your PhD project and how did you choose it? My PhD focuses on the role of long noncoding RNAs and the Tumour Microenvironment in High Grade Serous Ovarian Carcinoma. I considered a variety of factors when choosing my project. I compared the novelty of the research questions between each of my rotations. I also considered the resources that I would have access to, the research skills that I would learn and the ratio of computational to wet lab work involved. Furthermore, I tried to get the closest match between my learning style and my potential supervisor’s project management style.
How did you find the mathematical/computational component of the DTP? Coming from a background with minimal bioinformatics knowledge and skills, the taught bioinformatics module offered at Southampton University as part of the MRC DTP programme provided me with a solid foundation and reinforced my understanding of bioinformatics techniques, which I used in my rotations.
Do you have any publications? I contributed to Workforce Diversity: Let’s talk about race. I also have a pending publication.
Have you attended, presented a poster or spoken at any conferences? I attended and presented a poster at the 2019 EMBO/EMBL The Non-coding Genome Symposium, 16th - 19th October, in Heidelberg, Germany.
What have you enjoyed the most and the least about your experience so far? I was extremely pleased to learn that the MRC DTP programme offered PhD internships in conjunction with other organisations/industrial partners, both in the UK and abroad. My hope is that the opportunity for more internships develops to the extent that it becomes embedded in the MRC DTP programme, as an optional component, especially given that this will enable us to make informed decisions about our careers and increase our employability prospects post-MRC DTP.
About me: I am a pharmacist by trade who was lured by the bright lights of the laboratory, the excitement of research, and by a fascination with biology. Following a long-standing desire to pursue research, I completed an MSc in Cancer and Molecular and Cellular Biology at Barts Cancer Institute during the 2016/17 academic year, which not only built my base knowledge of molecular biology, the disease of cancer, and modern immunotherapies, but it also heightened my desire to pursue research at a higher level through a PhD. Having seen first-hand the brilliance of the scientists and expertise at Barts, it was a no-brainer to apply for their 4-year MRC-funded DTP. Additionally, having now completed my first rotation, I am determined more than ever to dedicate myself to these studies; the atmosphere in the medical school is contagious!
How did you find the mathematical/computational component of the DTP? The Quantitative Cell Biology module at Southampton was a fantastic introduction to bioinformatics, coding, and R Studio. Previously, I had never analysed large datasets or attempted any coding, and so this was a completely new skillset for me to develop. It is evident that this is a must-have skill for the modern biologist in the era of ‘Big Data’, where datasets of ever-increasing size and complexity are becoming commonplace in the laboratory. Therefore, exposure to this expertise at Southampton throughout the beginning of the DTP has been a privilege, gifting us a necessary vital edge.
Do you have any publications? I have no publications to date; however, I have had two abstracts published in the Journal of Investigative Dermatology. These are as follows: iRhom2-mediated immune dysregulation: Impact on the skin and oesophagus, May 2019, Volume 139, Issue 5, Supplement, Page S78 (2nd Author); and Type 2 Immunity Linked to iRhom2 and Tylosis with Oesophageal Cancer, September 2019, Volume 139, Issue 9, Supplement, Page S287 (1st Author).
Have you attended, presented a poster or spoken at any conferences? In 2019, I attended the following conferences: Keystone Symposia: Skin Health and Disease: Immune, Epithelial and Microbiome Crosstalk, Hannover, Germany, April 8-11. Here, I presented both a poster and a short talk. Additionally, I received a travel grant from the ESDR to attend this conference for the value of €1000; 49th ESDR meeting, Bordeaux, France, 18-21 September. Here, I presented a poster as part of a poster walk; and William Harvey Day at Queen Mary University of London where I presented a poster.
Have you completed any additional training? I have obtained my animal licence, and I have also visited the Gilliet lab in Lausanne where I learnt how to perform the tape-stripping skin wounding protocol.
What have you enjoyed the most and the least about your experience so far? The most enjoyable aspect so far has been to delve into new exciting areas of biology and research. The least enjoyable aspect has been the flipside; that the rotations are short and you have to move on, even when progress in an interesting area is being made.
What is your PhD project? I am based in Dr James Whiteford’s group in the Centre for Microvascular Research within the WHRI. My PhD project is on angiogenesis (the development of new blood vessels from pre-existing vasculature) in the context of eye diseases, such as Diabetic Retinopathy. I am currently focusing on the protein-type tyrosine phosphatase receptor CD148, to determine whether by targeting this we could halt the disease progression in eye diseases where angiogenesis is a feature.
I enjoy working in my lab, it is a supportive and sociable environment.
Do you have any publications? I was involved in, and so am named on, the review 'Syndecan-3 in Inflammation and Angiogenesis.'
Have you attended, presented a poster or spoken at any conferences? In the last year I have attended two conferences. At the September 2019 British Society for Matrix Biology meeting “Cell Adhesion Networks in Health and Disease” I presented a poster on my latest research.
Have you completed any additional training? In November 2018 I completed the Home Office course to gain my personal license.
What have you enjoyed the most and the least about your experience so far? My favourite experience so far on the DTP has been meeting other members of my cohort in Southampton in February 2019 and learning more about them and their research. My least favourite experience was when I first started and attended the Christmas meet and greet in December 2018, as I had no idea what the programme was about nor who the other people in attendance were, so it was very disorientating. Fortunately, since attending the Southampton Away Day in February 2019, other aspects of the DTP were introduced to me through other students on the programme.
What is your PhD project? My PhD project is entitled “Application of circulating tumour cell (CTC) analysis to monitor and predict prostate cancer response to Docetaxel.” So far, the project involves isolating CTCs from patient samples and performing number counts before, during and after treatment, as well as RNA/protein analysis to determine differential expression of genes involved in resistance - with the view to develop a non-invasive liquid biopsy method of monitoring and predicting treatment response in a patient specific manner. The company ANGLE plc are involved in my PhD project.
How do you think having a relationship with a company already at this stage of your PhD will help your career development? It’s a great opportunity to gain understanding of scientific research outside of academia, and to forge new professional relationships with people outside of the BCI. I will hopefully learn new, translation techniques that I can’t learn elsewhere that will aid my own research.
What have you enjoyed most about your experience so far? I have most enjoyed learning and improving my skills as a scientist, and meeting new and interesting people.
What is your PhD project? I am based in Dr James Whiteford’s group in the Centre for Microvascular Research at the WHRI and my PhD project currently is in arthritis investigating the mechanisms involved fibroblast invasion and destruction into cartilage and how to target these for therapeutic treatment focusing on the relationship between syndecan-4 and PTPRsigma.
What skills have you developed so far? I have developed a range of skills so far, ranging from laboratory based techniques such as adhesion and phagocytosis assays. I hope to further develop my skills in transfections and in vivo models.
What have you enjoyed most and least about your experience so far? So far, my favourite experience has been meeting the people on the programme and hearing about their research. My least favourite experience has probably been my transfer from one lab to another.
What is your PhD project? My project is looking at “Understanding human epidermal Langerhans cell tolerogenic function using systems biology” and centres around skin-resident Langerhans cells (LC) and the critical role they perform to coordinate skin immune responses and maintain immune tolerance. Dysregulation of tolerance at the skin can contribute to disease, emphasising the importance to further understand the mechanisms underlying LC immune regulation.
What skills have you developed so far? I have developed skills in cell culture, processing human skin samples, flow cytometry and FACS, Drop-seq, molecular methods (cDNA library processing for sequencing and qPCR), bioinformatic analysis using R and mathematical modelling methods (signalling Petri nets). I aim to further expand my skills using mathematical modelling during the remainder of my PhD.
How did you find the mathematic/computational component of the DTP? The DTP introduced me to computational biology with the first-year quantitative cell biology module and bioinformatic rotation projects. This has subsequently become a major element of my PhD research project. I am therefore very grateful that the DTP has given me the opportunity to learn these new skills and explore and appreciate an area of biomedical science I may have not shown interest in previously.
Have you attended, presented a poster or spoken at any conferences?I have attended a variety of conferences during my time on the programme. Most recently I have attended the 16th International Workshop on Langerhans Cells (2019) where I gave an oral presentation (travel bursary awarded); the British Society for Investigative Dermatology Annual Meeting 2019 where I gave an oral presentation (travel bursary awarded); and the University of Southampton Medical and Health Research Conference 2019, where I won the award for the Best Oral Presentation.
Did you carry out any additional training? I was a Biotechnology YES Young Enterprise Scheme competitor in 2017, for which I was awarded a BBSRC sponsorship. I attended the In Silico Systems Biology Course in 2017 at the European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus.
Do you have any publications? I am first author of a preprint entitled 'Single cell transcriptomic analysis indentifies Langerhans cells immunocompetency is critical for IDO1- dependent ability to induce tolerogenic T cells.' bioRxiv (2019).
About me: Before commencing the MRC-DTP course I obtained my undergraduate degree in Biomedical Science from Oxford Brookes, a Masters in Cancer Therapeutics here at Barts and spent two years working as a researcher in the Institute of Cancer Research, London.
What is your PhD project and how did you choose it? I chose to continue my final rotation in Molecular Oncology at BCI in the Martin lab as my PhD project. In this project, we aimed to establish the precise impact of DNA repair loss and DNA damage on PD-L1 expression and ultimately sensitivity to immune checkpoint inhibitors, and how this can be exploited therapeutically. I chose this particular project not only because I am fascinated by the research, but also because I felt like I would work well within the supportive and knowledgeable team and within a diverse and friendly large department.
What skills have you learnt so far? I have developed many skills throughout my MRes rotational year, which I would not have otherwise gained. New skills include InCell imaging, cloning, FACS and Flow Cytometry, Confocal Microscopy, tumour digestion and establishing primary cell cultures. I also have built upon existing skills and have had the opportunity to share these with members of my teams.
As my PhD unfolds I will gain more experience, namely in Mass Spectrometry. I also have had the privilege of gaining a sponsored CASE studentship from Astra Zeneca, who are interested in developing my project, providing me with the opportunity to work with them alongside the BCI.
Have you attended, presented a poster or spoken at any conferences? I recently attended the Gordon Research Conference on DNA damage, mutation and cancer in Ventura, California USA. I presented a poster titled: 'Identification of DNA mismatch repair mutational signatures that predict response to immune checkpoint blockade.' I’m also attending an EACR conference on DNA damage responses and cancer in Cambridge in April 2020, where I’m also presenting my poster.
About me: I initially studied Biology at Aberystwyth University and really enjoyed the immunology and microbiology modules, realising that immunity and infection was the field that really captured my interest. Time spent in the lab for my dissertation project really showed me that I loved doing research, so I decided to pursue a PhD, which led me to the MRes PhD at Southampton University.
What is your PhD project and how did you choose it? My PhD project is ‘Investigating Host Pathogen Interactions in the Asthmatic Airway.' This project was extremely appealing to me as it encompasses both fields of Infection and Immunity, which are where my interests lie. Southampton is renowned for both respiratory and translational research, which is of course important as at the end of the day, our research aims to improve patient outcomes and quality of life.
What skills have you developed so far? During this PhD I have developed a variety of laboratory techniques including primary human and bacterial cell culture, in vitro infection assays, flow cytometry, qPCR, FISH, ELISA, gentamicin protection assays and cell cytotoxicity/proliferation assays. I have also been able to build on the skills learnt during the computational taught module by analysing a RNASeq data set that I generated as part of my project.
Have you undertaken any additional training? I have had additional training on IRIDIS, the University of Southampton high performance computing system, which is required for analysis of large data sets.
How did you find the mathematic/computational component of the DTP? The computational component introduced me to big data sets and the different ways of analysing such data. This was incredibly useful as a huge component of my PhD was to generate and analyse an RNASeq data set.
Have you attended, presented a poster or spoken at any conferences? I have attended several internal and external conferences, most recently including: the ERS Lung Science Conference, Estoril, Portugal (March 2019) and the Southampton Medical & Health Research Conference, Southampton (June 2019) where I gave thematic poster presentations; and the ERS International Congress, Madrid, Spain (October 2019) where I gave a poster discussion presentation. I won the British Association for Lung Research (BALR) travel award twice to attend the ERS International Congress in 2017 and 2019.
Have you won any prizes for your presentations? I won the ‘Best Poster Presentation’ Prize at the Southampton MedConf 2019 and ‘Outstanding Poster Prize’ at the Network for Anti-Microbial Resistance and Infection Prevention festival 2019.
What have you enjoyed the most and the least about your experience so far? I have really enjoyed the opportunity to develop my skills as a scientist through a combination of the lab rotations, taught modules and additional training courses provided by the IPhD programme. The nature of the IPhD also allows you to be able to interact with your cohort and other research groups, which helps you to establish a professional network that is crucial going forward in your scientific career. In addition, the IPhD Away Days give an excellent opportunity for all students to present in a safe and friendly environment, which allows you to see the breadth of research your fellow students are undertaking.
What is your PhD project and how did you choose it? I continued with my third rotation for my PhD, entitled “Role of oncofetal glycosaminoglycans (OFGAG) for the immune privilege of pancreatic cancer,” which looked at developing a new CAR-T cell for the treatment of pancreatic cancer. During the rotation I isolated primary human T cells from blood, performed PCR and lots of molecular biology to clone the constructs into a plasmid and performed cytotoxicity assays.
It was really hard for me to choose as I enjoyed all of my projects, but I chose this one because I am really interested in CAR-T cell therapy and liked the translational theme of the project.
How did you find the mathematic/computational component of the DTP? I think the bioinformatics part of the course was really valuable to me as it has allowed me to have a better understanding of what is possible to find from large data sets that already exist. Using the skills I have developed, I have been able to do some work independently and I hope to develop my skills further to incorporate more bioinformatics into my project in the future.
Do you have any publications? Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma. Pancreatology (2020) pii: S1424-3903(20)30042-9. PMID: 32173257; A Day in the Life: 6 Cancer Researchers in 6 Different Countries; Standing up for Science – A Voice of Young Science Workshop.
Have you attended, presented a poster or spoken at any conferences/meetings? I was selected to attend a Voice of the Future event as a member of the Biochemical Society where I was part of a televised question time style interview of members of a Government Select Committee (13th March 2018). I attended an Art and Science workshop held by the biochemistry society in collaboration with UAL (27th March 2018). I presented a poster at the London Pancreas Workshop in May 2018. I presented a poster at the BACR student conference in November 2018. I was invited to a Stand up for Science workshop in Manchester about science policy (April 2018). I am also a STEM ambassador and volunteer at the Centre of the Cell, working with school children learning about science.
Have you completed any additional training? I have got a Home office licence and I have completed phlebotomy training.
What have you enjoyed the most and the least about your experience so far? My experience of the DTP program has been really positive, I have met a lot of really great people and been allowed to develop a wide range of skills. I have really enjoyed the extra courses and teaching provided by the course, for example the media training day. One of the less enjoyable parts of the course was the first term when we had a lot of coursework and teaching in combination with the lab project, which made planning your time difficult. Overall I’m really happy I chose the DTP program at Barts and I am loving my PhD.
About me: I did my undergraduate degree at Queen Mary in Medical Genetics. I decided to apply for the Southampton MRC DTP Cancer Pathway, as I thoroughly enjoyed the immunology and cancer biology modules that were offered on my undergraduate course, and was intrigued by the field of cancer immunotherapy.
What is your PhD project and how did you choose it? My PhD project is entitled 'Vaccine Strategies to Target the Cancer Mutanome' and it explores how tumour-specific mutations can be exploited to develop more effective vaccine-based immunotherapeutic strategies. I chose to continue my first lab rotation for my PhD as I found the team supportive, the project fascinating and liked the balance between the dry and wet lab work involved.
What skills have you developed so far? I have learnt a variety of skills so far - molecular biology, PCR, tissue culture, epitope prediction, ELISpot, in vivo work, DNA and RNA transfections, nuclofection and FACS, basic bioinformatics and understanding of genomics and transcriptomics data, basic understanding of R, in vitro mRNA synthesis. In the future I hope to develop a better understanding of genomics and transcriptomics analysis and tumour dissociation. I have had some additional training on immunology and using the high performance computing system at Southampton.
How did you find the mathematic/computational component of the DTP? The computational component on the DTP has been very valuable. It has given me a greater understanding of large data sets. I have also had the opportunity to familiarise myself with various packages on R, which I am using in my PhD. This experience was extremely useful in introducing me to coding, and analysing genomics, transcriptomics and proteomics data. It was also extremely useful in helping me understand when to use various statistical tests.
Have you attended, presented a poster or spoken at any conferences? I have attended a variety of conferences throughout my time on the programme. I have delivered poster presentations at these conferences, including at the Southampton Medical and Health Research Conference (2017), the Cancer Sciences Unit Conference, the 2nd Annual Next-Gen Immuno-Oncology Congress and the Southampton Medical and Health Research Conference. I gave an oral presentation on Targeting mutanome in multiple myeloma at the 11th Cancer sciences Unit Conference. I won the prize for Best Poster at the Wessex Immunology Group Annual Spring Meeting in 2017.
Have you won any other awards? I was awarded Third Place at the Faculty of Medicine 3 Minute Thesis in 2019. I have also won an internship by the Academy of Medical Sciences to work with the UKRI Medical Research Council Policy Team.
What is your PhD project and how did you choose it? I chose to continue my third rotation- “Identification and interpretation of pathogenic noncoding mutations in pancreatic cancer”- as my PhD project. I am currently using bioinformatics to look at publicly available ChiP-seq and matching RNA-seq data to find hotspots of pathogenic non-coding mutations in active gene regulatory regions. Not only is this a subject area I am very interested in, the PhD also involves learning new bioinformatics and laboratory techniques that I have not used before and will be useful in the future.
How did you find the mathematic/computational component of the DTP? The mathematic/computational component of the DTP programme and taking bioinformatics rotations has definitely helped me with the bioinformatics part of my PhD project.
Do you have any publications? I have contributed to two publications during my PhD: The Identification and Interpretation of cis-Regulatory Noncoding Mutations in Cancer (Review). High-Throughput (2018) 8(1). PMID: 30577431; Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study. PLOS Medicine (2017) 15, 10. e1002694. PMID: 28715416
Have you attended, presented a poster or spoken at any conferences? I attended the National Cancer Research Institute conference in November 2018. I presented a poster at the Somatic Evolution and Tumour Microenvironment Symposium at the Francis Crick Institute on 2nd Dec 2019.
Did you carry out any additional training? I attended a course in Python programming language in October 2017.
What have you enjoyed the most and the least about your experience? Overall I’ve enjoyed the varied experience I have gained rotating through three different laboratories and meeting new people. I have least enjoyed presenting my work, however, this is necessary and good experience.
The DTP and PhD has been enjoyable and challenging. I have learnt/developed many transferable skills and new laboratory techniques with the support of my supervisors and fellow colleagues.
About me: After graduating from my BSc in Biomedical Science, I spent a couple of years working as a technician in the NHS to build up my confidence in the lab, before applying to Southampton. I knew I was interested in cancer immunology, but little more than that. Despite having no bioinformatic background, I also want to move into a career involving bioinformatics, so I have been learning by doing during my PhD. Now I have established myself as my group’s go-to Bioinformatician, constantly improving my skills through real-life problem solving.
What is your PhD project and how did you choose it? My project is to identify novel cancer vaccine targets, which can be utilised in an oral cancer vaccine. I wasn’t sure what sort of project I’d work on when I started, but during the initial iPhD lab rotations I found a particular interest in cancer vaccines, and identified an approach I could take to employ bioinformatics to contribute to an ongoing project.
What skills have you learnt so far? Bioinformatics mostly, including all sorts of big data processing and analysis. I’ve also become a very confident presenter, happily speaking to groups and crowds about my work and my field. My science writing is markedly better than when I began, I can comprehend far more from fields both familiar and novel than before, and I’ve learned to work independently, forming my own ideas and acting upon them. A bit of everything really.
How did you find the mathematic/computational component of the DTP? The Quantitative Biology module at the University of Southampton was a good training in the basics of bioinformatics and data analysis. It sparked my interest and increased my confidence to steer my PhD studies into mathematical and computational biology, as an independent scientist.
What have you enjoyed most and least about your experience so far? Academic freedom has been amazing for me. Being free to create my own questions, and find my own way of answering them, is incredibly satisfying. On the flip side of that though, my least favourite part is the inevitable dead ends. When you spend weeks if not months working on an experiment only to find nothing of any value. It’s frustrating, but you just have to accept it as unavoidable.
How did you choose your PhD project? I spent my third rotation in Sarah McClelland’s research group and have chosen to continue this project as my PhD, entitled 'Development of a system to induce specific monosomies.' Our lab works on the underlying biology of the highly disrupted genomes of cancer, focussing on how huge alterations in chromosome structure and number are acquired and tolerated. When progressing from the MRes to the PhD, and choosing which lab to return to, I was looking for a group with a strong publishing record, expertise in techniques I was keen to learn, with projects spanning fundamental cell biology to translational work. For me, the McClelland group not only offered this, but also offered a project which I find interesting and am excited to work on, within a great team.
What skills did you develop during the rotations? Through the rotations, I developed varied lab skills from western blotting, cell culture, immunohistochemistry, molecular biology, microscopy, and experience with CRISPR/Cas9 systems. To complement this, the course is structured such that the taught modules run in parallel to rotations to give a core foundation in the theory of research methods and also computational biology. For me, the content on bioinformatics has been invaluable.
Do you have any publications? I have contributed to two review/comment publications during my PhD: Watching cancer cells evolve through chromosomal instability. Nature (2019) 570(7760):166-167. PMID: 31182831; The emerging links between chromosomal instability (CIN), metastasis, inflammation and tumour immunity. Molecular Cytogenetics (2019) 12: 17. PMID: 31114634
Have you attended, presented a poster or spoken at any conferences? At the beginning of my final year, I got the opportunity to travel to Paris for a conference where I gave a talk presenting my PhD work. This was made possible by a BCI travel bursary covering all expenses.
Do you have any additional comments about your overall experience? My experience of the course has been excellent throughout. The collaborative nature of the course between the two universities offers unique opportunities to benefit from expertise from leading researchers at both Queen Mary and Southampton. Then the course itself is structured so that the MRes gives you a strong foundation which sets you up in the best way to excel in your PhD research, both from the taught modules and your rotation projects which expose you to a wider set of laboratory techniques and put your research in context of the field. To anyone considering a PhD, I would 100% recommend this course.
What rotations did you undertake in your first year? For my first rotation project, I investigated the effect of double-stranded RNA on extracellular matrix deposition in an in vitro model of the airway mucosa. I chose this project as I was able to learn multiple wet lab techniques including human cell culture, transepithelial resistance, western blot, ELISA and immunofluorescence microscopy.
I chose to do a bioinformatics-based second rotation project, where I analysed the transcriptomic and epigenetic cytokine production by human skin Langerhans cells. I was able to utilise and further develop the bioinformatics skills I learned from the Quantitative Cell Biology module.
Following this, I knew I wanted my PhD to have elements of both wet lab techniques and bioinformatics in airway disease. I then decided to do my third rotation project on a subject that would then lead on to my PhD project. My third rotation project and PhD investigates the global response of mast cells by RNA sequencing. I was able to use my wet lab techniques to optimise the conditions for preparing the samples and studying mast cell responses. I am looking forward to using my bioinformatics skills to analyse the data from RNA sequencing.
Have you attended, presented a poster or spoken at any conferences? I presented my first rotation project as a poster discussion (2-minute talk followed by poster presentation) at the end of Year 1 when I attended my first international conference, European Respiratory Society (ERS) International Congress 2017, in Paris, France. I received the ERS Young Scientist Award for outstanding submitted written abstract, which included free registration and €600 to cover travel and accommodation.
I have presented a poster of my PhD at the ERS Lung Science Conference 2018 in Estoril, Portugal. I received an ERS travel bursary award for my submitted abstract to present in Portugal. The award included free registration, €600 and a mentorship lunch at the conference. I attended the European Mast Cell and Basophil Research Network (EMBRN) 2019 meeting in Uppsala, Sweden. I used my MRC conference allowance, along with €300 I won from Biolegend’s junior investigator travel award.
What rotations did you undertake during your first year on the programme? My three rotations were 'An in silico approach to deconvoluting whole-tissue biopsies of inflammatory skin diseases reveals a conserve cell-specific signature that infers local disease status' ; 'A bioinformatic approach to disease-specific signatures identified autoimmune modules associated with pulmonary tuberculosis' ; and 'Langerhans cells at different activation statuses show divergent antigen-presenting capability concomitant with increases in IRF4 levels.'
What did you choose as your PhD project? My PhD project is 'Investigating the cross-talk between structural and immune components of human skin to understand pathogen sensing in cutaneous health and inflammation.' Deconvolution of the cutaneous transcriptome from healthy and inflammatory skin conditions to investigate host expression in response to altered immune and microbial contexts. We aim to use single-cell RNAseq of reconstituted epidermis models to identify bacterial responses in keratinocytes to understand mechanisms underlying atopic dermatitis and psoriasis arising from host-microbiome dysbiosis and cutaneous inflammation.
I chose this project because of the computational biology aspect allowing me to further develop my bioinformatics skills and generating my own data in the wet lab. I really enjoyed working with the Systems Immunology Group for two of my rotations where I developed a keen enthusiasm for skin biology and bioinformatics, and had some fun along the way!
What skills have you developed so far? My undergrad background was molecular microbiology so my PhD project has really given me the opportunity to add human tissue culture such as developing reconstituted epidermal models and host-microbe co-cultures, and bioinformatics skills, such as coding, standard bulk and single-cell sequencing pipelines, and machine learning to my CV.
Do you have any publications? I am first author on the following papers: Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy dependent modification of the keratinocyte immunophenotype. MedRxiv (2019); Langerhans Cells-Programmed by the Epidermis. Frontiers in Immunology (2017) 8:1676. Review. PMID: 29238347; Gene Expression Signatures in Tuberculosis Have Greater Overlap with Autoimmune Diseases Than with Infectious Diseases. American Journal of Respiratory and Critical Care Medicine (2017) 196(5):655-656. PMID: 28753379.
Have you attended, presented a poster or spoken at any conferences? I have attended various conferences. The most recent ones were the British Society for Investigative Dermatology (2019) and the Faculty of Medicine Conference (2019) where I gave oral presentations.
How have you found your overall experience of the programme so far?I have really enjoyed my PhD, which I think is mainly down to choosing to do a DTP with an MRes at the start. This allowed me to get a feel for different research projects and groups, where I could develop a project with a PI and group I knew I would enjoy working with. Doing bioinformatics was really out of my comfort zone at the start but I have developed an exciting project with some good results and useful skills that should come in handy for a career in research!
What is your PhD project and how did you choose it? My PhD project is based at the Blizard Institute and is supervised by Dr John Connelly. My research focuses on developing a vascularised and immune responsive in-vitro skin model using 3D bio-printing. I chose this project because I was interested in broadening my knowledge of 3D culture models and I was excited by the potential impacts of this research on the fundamental understanding of skin biology, in the discovery and testing of therapeutics and in the engineering of tissues for regenerative medicine purposes. Additionally, my project is an industrial CASE studentship, which means that I have an industrial partner, Kirkstall Ltd. Towards the end of my PhD I will be conducting a 3-month placement within their Research and Development team. During this placement I will gain an insight into the biotechnology industry and gain knowledge about fluidic cell culture systems and their applications for different tissue and disease models.
What skills have you developed so far? So far during my PhD I have learned to print in-vitro vascularised skin models using the 3D-bioprinter and have further developed my skills in adherent- and suspension-cell tissue culture, immunohistochemistry, confocal and epifluorescence imaging and data analysis.
What is your PhD project and how did you choose it? My PhD project focussed on the development of cell-based assays to study Fc gamma receptors – the cellular receptors for antibody molecules. I was originally attracted to Southampton because of its impressive reputation for research in the field of immunotherapy. Moreover, the fact that the project had a company collaboration with Promega and therefore the opportunity to work in the USA was an advantage.
What skills have you learnt so far? During my PhD, I was able to build on my molecular biology skills and learn to perform a range of cell-based assays. I also had the opportunity to develop my presentation skills in countless meetings, journal clubs, and integrated PhD away days. Being part of a large group also provided me with skills in communication and teamwork.
How you think having a relationship with a company already at this stage of your PhD will help your career development? As well as being on the integrated PhD pathway, I was also lucky enough to have an industrial Collaborative Award in Science and Engineering (iCASE) studentship. This meant that the life sciences company, Promega, jointly funded my project. This gave me the opportunity to present my work to industrial collaborators regularly. Towards the end of my PhD, I also had the opportunity to complete an internship in the Research and Development department in the USA at Promega HQ. This allowed me to apply results that I had obtained in Southampton to the development of a new cell line, learn some new skills and gain interesting insights into how companies operate. Overall, having a company collaboration provided me with very useful experiences and contacts for the future.