National Eye Research Centre, U.K. funds VISICORT exploitation research
VISICORT PIs Professors Malcolm Walkinshaw (University of Edinburgh) and Conor Murphy (RCSI, Royal College of Surgeons in Ireland) and Dr Karl Burgess and Lisa Imrie were recently awarded funding (£66,500) from the National Eye Research Centre (U.K.), (NERC) for the research project: A Multi-omics approach to eye tissue characterisation in Keratoconus & Fuch’s Dystrophy patients. Congratulations to the team and in particular to Lisa who has pioneered the use of a multi-omics approach in analysing eye tissues.
The fully-funded PhD project will examine two common conditions affecting the cornea – keratoconus and Fuch’s endothelial corneal dystrophy (FECD). Lisa, a proteomics specialist will identify families of proteins, lipids, and metabolites (“multi-omics”) using mass spectrometry – an instrumental method looking at the chemical composition of substances. Analysing different eye tissue samples from the same patient at different time points will allow for a better understanding of how these diseases develop and progress. The research will benefit from access to a collection of more than 3000 biosamples from people with either keratoconus or FECD that have been enrolled in the VISICORT cross-sectional analysis study, where the different eye tissues have been stored and linked to a clinical database with detailed information about each patient.
“It is really gratifying to see how the VISICORT project has led to the development of a new and exciting approach for analysing the invaluable collection of our biological samples. We can look forward to being able to identify important new and medically important biomarkers from Lisa’s VISICORT-inspired PhD.”
Professor Malcolm Walkinshaw, University of Edinburgh
The 3-year project will also draw upon the VISICORT network of clinical and scientific experts in the field of corneal disease. This work will identify signalling and metabolic pathways that are clearly implicated in keratoconus and FECD disease aetiology. Lisa aims to get started on October 1, 2020.
NERC, the National Eye Research Centre (https://www.nercuk.org/) is a charitable incorporated organisation and community of donors, volunteers, researchers, healthcare professionals, and fundraisers working together towards a common goal of beating sight loss forever. They fund pioneering research into the causes of eye disease to develop better prevention methods and more effective treatments for children and adults. NERC has been able to invest over £17 million in research projects that are bringing scientists ever closer to answering some of the most fundamental questions about eye health and eye disease.
Interview 2: Proteomics Specialist Lisa Imrie, U of Edinburgh offers a research career snapshot
In the 5 years since its launch, VISICORT has gathered a unique collection of biological samples from corneal transplant recipients across 5 European countries. We are especially motivated to ensure that the generosity of these patients has a legacy of new research that continues to grow beyond the life-time of the project itself. Lisa’s exciting PhD project is a perfect example of this potential. I am particularly proud that we have been able to attract a talented scientist at the University of Edinburgh into the field of corneal transplant biology and that her research has the potential to directly benefit patients with corneal disease in the future.
VISICORT Coordinator, Professor Matthew Griffin
Lisa Imrie is a Proteomics Specialist at the University of Edinburgh and a graduate of Edinburgh Napier University with a degree in microbiology and biotechnology. She has recently started her PhD studies taking a unique perspective in the analysis of biosamples from the VISICORT Foundation Biobank.
In this interview (2 of 2), Danielle Nicholson, Pintail Limited poses questions to Lisa about her work in proteomics, what a career in laboratory science really looks like and her PhD research.
What is proteomics and how did this become an interest for you?
Proteomics is the large-scale study of proteomes (a set of proteins produced by an organism/system). It can be used to investigate when/where proteins are expressed, protein production rates, protein modifications (e.g. PTMs), protein-protein interactions, and how proteins are involved in metabolic pathways, amongst other things.
I first became interested in proteomics between the third and fourth year of my undergraduate degree. I worked for the summer in a local research institute in what was then their “Functional Genomics Unit” which had one mass spectrometer which I used to identify proteins that were present in researcher’s samples by peptide mass fingerprinting. I was then invited back to complete my honours project within the same unit and that’s when I was hooked. As luck would have it, on the completion of my honours project a position came up within the expanding unit that I successfully applied for and thus began my career in mass spectrometry and proteomics.
What are your main goals as a PhD researcher?
One main goal of this project is to identify clinically useful biomarkers in eye disease patients. To this end, I will use mass spectrometry instrumentation to identify proteomic, metabolomic and lipidomic markers in different eye tissues across both keratoconus and FECD. This will be the first time in ophthalmic research that this combination of omics data sets will be integrated to provide a better understanding of the disease mechanisms of these corneal diseases.
Another goal is to build as wide a knowledge base as possible around my chosen topic. Every day I’m learning more and more and each new fact will undoubtedly lead to more research down a different avenue. Compiling all this information to give me the best chance of successfully completing this project will be an ongoing effort.
“I love immersing myself in the literature related to this topic, applying it to my own work and theories and seeing what direction my research will take me in on a daily basis!”
Lisa Imrie, PhD candidate at the University of Edinburgh
Give us a snapshot of your work environment and day.
I work in the Kings Buildings campus of the University of Edinburgh. There are many campuses across the city and we’re based on the south side. All of Science and Engineering (including the School of Biological Sciences where I work) are based on this campus. The facility I work in is called EdinOmics and there are currently four staff members who work here: an academic leader, a metabolomics specialist, a proteomics specialist (me) and a lab manager. Our mass spectrometry lab is situated on the ground floor and we all have offices dotted about the building. I have an office just opposite the lab which is great for popping in and checking on the status of all the instruments and generally keeping an eye on things. For all sample preparation, we have a wet lab on the first floor which has all the general lab equipment you’d expect to see in any biological lab. Within our building, there are six different research groups and we all share the same wet lab, however, our mass spectrometry lab is just dedicated to the EdinOmics group and the instruments.
Describe your typical day. What do you do? What skills do you need?
A normal day for me would start with arriving at work at around 8.30 and heading straight to the mass spectrometry lab. The first thing I like to do before anything else is to check that the instruments are working as expected and there are no blinky red lights on anything – not good news! If there have been samples run the previous day or through the night I’ll start the data analysis for them which will involve the files being converted into a database searchable format which can take a little time. Whilst this is ticking over I’ll head to the office and switch on my PC before making myself a cup of coffee. My day will then consist of any combination of:
· Data analysis from samples run the previous day/overnight
· Reporting of results to clients either by email or in person
· Meeting with potential clients who are interested in using the facility to answer their research questions
· Any general lab maintenance requiring attention
Throughout all this, whenever I have time, I will focus on my own PhD project. At the moment this will include the ongoing literature search to broaden my knowledge of the topic and keep up to date with what’s been achieved in the field so far as well as planning any pilot experiments to work up the methods I plan to use throughout my project. All this juggling requires a lot of time management skill and it is definitely one of the most difficult parts of my job. Finding time for both running the facility and my PhD project can be challenging!
What are your main interests outside science?
I have a young family (11yr old daughter and 7yr old son) so my interests outside of work revolve mainly around them! They definitely have better social lives than I do and between my husband and myself, we spend most of our time taxiing them around to various clubs/sports. It’s great to see them grow into confident young people so I wouldn’t have it any other way. If I manage to get a minute to myself I like to socialise with family and friends and put the world to rights over dinner & drinks.
What advice would you give to a young person wanting to pursue a career in science?
Keep an open mind and don’t try to “specialise” too early. I went from an interest in marine biology to microbiology to biotechnology and ended up working with mass spectrometers in the omics fields. Similarly, don’t be scared to branch out even when you have decided on your field of interest. If someone had told me a couple of years ago that I’d be doing a PhD related to ophthalmology I would have laughed at them. It’s amazing where a career in science can take you!
Sum up what you find most interesting about your work now in just one sentence.
I love immersing myself in the literature related to this topic, applying it to my own work and theories and seeing what direction my research will take me in on a daily basis!
Interview: Lisa Imrie, U of Edinburgh uses the VISICORT Biobank
Lisa Imrie is a Proteomics Specialist at the University of Edinburgh and a graduate of Edinburgh Napier University with a degree in microbiology and biotechnology. She has recently started her PhD studies taking a unique perspective in the analysis of biosamples from the VISICORT Foundation Biobank.
Danielle Nicholson, Pintail Limited caught up with Lisa Imrie after the latest plenary meeting in Galway to pose a few questions about her PhD research. In this interview (1 of 2), Lisa discusses her PhD project, how new techniques in the lab and with the data set analyses will carry the results of VISICORT forward and contribute to the field of proteomics.
What is the main focus of your PhD project?
To characterise different eye tissues and identify clinically relevant biomarkers in both keratoconus and Fuch’s Endothelial Corneal Dystrophy (FECD) using a multi-omics approach.
Why have you focussed on that in particular? What is it that interests you about it?
Until recently my career has been very technically orientated as I currently provide a proteomics service for a mass spectrometry core facility within the University of Edinburgh. This has allowed me a brief snapshot of other researcher’s work however I’ve never had any biological research of my own to focus on. In 2015 I was charged with helping the groups postdoc, Khadar Dudekula, with her proteomics profiling of eye tissue samples from the VISICORT project. This area of research piqued my interest and from becoming more involved in the sample analysis and also attending the plenary meetings it became apparent that there was massive scope to carry this research forward in any number of directions. Within my facility, I have a number of high-end mass spectrometers that can carry out various “omics” analyses so this PhD project seemed like a golden opportunity to utilise them to analyse the large number of samples available to me within Biostor Ireland. There are thousands of samples within this biobank so it was sensible to narrow down my thesis question and focus on looking at a couple of conditions to start with (keratoconus and FECD).
“It is really gratifying to see how the VISICORT project has led to the development of a new and exciting approach for analysing the invaluable collection of our biological samples. We can look forward to being able to identify important new and medically important Biomarkers from Lisa’s VISICORT-inspired PhD.”
Professor Malcolm Walkinshaw, University of Edinburgh
What big questions do you want to answer?
I want to characterise keratoconus and FECD using a multi-omic approach combining proteomic, metabolomic and lipidomic analyses. This will include developing a method for the efficient extraction of lipids, metabolites and proteins from a single sample, enabling the targeted and untargeted analyses of each eye tissue. Extracting multiple “omes” in one step will ensure like for like comparisons and give a genuine snapshot of the biological status of the system. This will result in much better correlations between differences in metabolites/proteins and we can obtain greater insights into the metabolic pathways comparing healthy and disease states through interrogation and integration of the different omics datasets. This method will be unique in eye tissue omics studies to date.
What are the biggest obstacles to answering these questions?
My biggest challenges in this project will be all the sample prep method development. I’ve seen a similar one-step extraction method used before on plant material but never on the eye tissues that I’ll be working with. All the different tissues, e.g. tears, aqueous humor, cornea, all have very different compositions so it’ll be interesting to see if the one method works with all sample types.
Another challenge I’ll face is the data integration and interpretation. To date, I have only ever run single omics experiments which require just one software analysis approach. I’ll now have to find a way to integrate all the data generated from the proteomics, metabolomics and lipidomics analyses. Fortunately, there’s a symposium towards the end of the year which deals with Multiomics data integration that I’ll be attending so hopefully this will give me some idea of the best way to deal with these large datasets.
How has VISICORT contributed to your project concept and research?
Without VISICORT it may never have occurred to me to embark on my own PhD project. Because the subject matter interested me so much and due to the large number of samples available in the Biostór it was an easy jump to design a project to expand on the profiling data already generated by mass spectrometry. The challenge was distilling it down to look at a couple of biological questions as there were a large number of avenues we could have pursued. The two plenary meetings I have presented at, the first in Berlin to pitch the idea of the PhD project and the second in Galway to present a more definite structure, have been invaluable to me. Getting advice and suggestions from experts in the field has definitely shaped my work going forward.
VISICORT Foundation Biobank is available for use
The VISICORT Foundation Biobank (VFB) of tears, peripheral blood mononuclear cells, plasma, aqueous humour and donor and recipient corneal tissue samples is available to academic researchers, applied research institutes and pharmaceutical research centres for eye disease research purposes. For more information and to make enquiries, please see our brochure.
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This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602470. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.
