Early-career grants: funding to get the all-important first proof of concept

The Society for Endocrinology provides early-career grants to support its members in a number of ways. In this article, Kerry McLaughlin explains how the grant helped her search for an elusive autoantigen, which made a splash on the BBC news page earlier this year.

Dr Kerry McLaughlin PhD JDRF Research Fellow
Dr Kerry McLaughlin, JDRF Research Fellow

 People who have type-1 diabetes lose the ability to control blood sugar levels because of the destruction of insulin-producing cells in their Islets of Langerhans. We know this is because the immune response targets four specific proteins (known as autoantigens), and while the fifth major autoantigen has been known to exist for over 20 years its identity was unknown.

Technical limitations at the time made it impossible to identify the fifth autoantigen, but we used a combination of biochemical techniques alongside high-tech mass spectrometry to discover that this fifth major autoantigen was tetraspanin-7, at last providing a complete picture of the immune targets in type-1 diabetes.

This discovery can now be used to help identify those at risk of future disease development through the detection of antibodies to tetraspanin-7, and to further research into strategies aimed at blocking the immune response to the major autoantigens in order to prevent the disease altogether.

This research came about as a result of work we were doing with a separate autoantigen (IA-2). My postdoctoral supervisor, Dr Michael Christie, was involved in earlier efforts to identify the fifth major autoantigen, and we realised that we could apply the technology developed for IA-2 for this purpose.

This was where the Early Career Grant from the Society for Endocrinology came in and provided some much needed resource to kick-start the project. While it took a little bit more time and effort to finally identify tetraspanin-7 as our elusive fifth autoantigen, this early funding was instrumental to the project’s successful completion.

I have since been awarded a 3-year fellowship by JDRF to continue my research into tetraspanin-7 in the laboratory of Professor Patrik Rorsman FRS, FMedSci at the University of Oxford. We published our study in Diabetes, and it was covered in the mainstream media by the BBC, at one point trending in the top 10 news articles, as well as by the Huffington Post. It was great to have the opportunity to share our research with the wider public, and I was very motivated to see how interested people were in hearing about scientific advances.

For young researchers, getting enough preliminary data to put together a competitive grant application for a major funding body can be tricky. The Early Career Grant from the Society for Endocrinology provides postdocs with the opportunity to explore a new avenue of research and can be used to provide that all-important first proof-of-concept.

The second advantage to this scheme is that it gives early-stage researchers a chance to go through the process of preparing an application for funding as well as managing an award,  but on a much smaller scale and without the heavy administrative burden of larger grants. I would certainly recommend the scheme to those keen to take the first step towards an independent career in research.

Kerry McLaughlin, originally from Cape Town, South Africa, was awarded her PhD in Immunology from King’s College London in collaboration with The Pirbright Institute. She then spent six years as a postdoc in the laboratory of Dr Michael Christie at King’s College London before taking up a JDRF fellowship at the University of Oxford in 2016.

For details on how to apply for our Early Career Grant, visit our website. The next deadline for applications is 27 November 2016.

SfE BES – Call for abstracts!

The annual Society conference, SfE BES, takes place this year in Brighton on 7-9 November 2016. It’s a great chance to network with colleagues, showcase your work and explore new research in your area of endocrinology. Our programme of events is varied yet specific – bringing together the best of basic science, clinical investigation and clinical practice, you have the chance to expand your horizons into other parts of the field whilst also attending those lectures which are really specific to you.

The submission system for abstracts is open until midnight on Wednesday 22nd June – so you have more than enough time to polish your final abstract and send it along. It’s not just a chance to show your colleagues across the whole field of endocrinology what you’ve been working on – it’s a chance to tell them why what you’ve been working on is important.

Last year at SfE BES, a great programme highlight was a session entitled ‘Evolving model systems for complex tissues’, which was chaired by Kevin Doherty and Shareen Forbes. In the ’90s, manipulation of human embryonic stem cells (hESCs) was something of a new thing. It was anticipated that the ability to grow human tissues in culture using hESCs would provide incredible model systems for drug development, toxicity testing and cell therapy.

However, it wasn’t until 2005 that reliable markers had been developed and a significant number of important signalling pathways had been elucidated in the path to differentiation. By this point, some ten years later, finally a tool box existed for nearly every tissue type. This lead to some of the first clinical trials, using pluripotent cells to treat age-related macular degeneration. However, liver disease, diabetes and neurodegeneration were still elusive and challenging goals.

By 2014, fully functional human beta cells has been generated, and they took only 45 days and 7 stages in culture. This was a hugely exciting moment for diabetologists and researchers across the world. But then, of course, the question sprang up: could they be used as a source of islet cells for replantation? Or would they merely serve as an invaluable model?

At Kevin and Shareen’s BES session, they gave a detailed overview of both the background to the field of complex tissue model systems, and the current state of basic science and clinical research, highlighting very recent advances, and discussing the potential future.

The stem cell field continues to expand rapidly. 2016 has already been the year that Chinese scientists grew functioning mouse spermatozoa from skin cells – these went on to fertilise egg which developed into embryos and grew to successful progeny. What will the second half of 2016 bring?

With over 1000 delegates, 100 abstract lectures, 10 plenary lectures, and an evening of awards and prizes, SfE BES is the best place for you to spread the word on your research, and meet the colleagues that you want to work with in future. Your lecture might be the one were talking about all the way into June 2017.

So submit your abstract now through our submission system. Submissions close on Wednesday 22nd June at midnight.brighton 2

See you in November!

Awareness of BRCA2 gene mutations in men becoming women

A recent case study in Endocrine-Related Cancer describes the case of a transgender woman developing breast cancer linked to a mutation in the BRCA2 gene. In this post Dr Adrian Daly talks about the potential implications of their findings – and what it could mean for screening techniques.

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Few medical issues have seen greater changes in public awareness recently than those related to transgender individuals.  Discussions around transgender identity were previously marginalized.

In contrast, today it is front and center in debates related to equality in many countries.  Along with the work of activists, the arts and media have played a central role in this radical change in openness regarding transgendered people and their experiences.  Leading characters in mainstream television drama are played by transgender actors such as Laverne Cox in Orange is the New Black, while popular series like Transparent have the transgender experience as the main theme of the show.

The real life experiences of gender transformation of the former Olympian and reality TV star Caitlyn (formerly Bruce) Jenner have been chronicled intimately. The upshot of this has been to dispel many taboos about discussing transgender related issues in the mainstream media.  This, in turn, improves awareness around these issues and how transgender is managed.

Endocrinologists play a key role in this specialized area of medical care.  Cross hormonal therapy is a cornerstone of gender transformation and is responsible for many desired changes sought by patients.  For male to female transformation, this involves taking doses of female hormones like estrogens and blocking male hormones with anti-androgen therapy.  This process leads to important physical changes like breast growth.

Hormonal therapy not only brings welcomed transformations but also changes in screening activities.  Male to female transgender individuals should learn and adopt breast examination and routine mammography similar to genetic females.  While male to female patients treated with hormones don’t appear to have an increased risk of breast cancer, there is a risk factor in this condition that might need better awareness in patients and doctors alike.

As published on 21 March 2016 in Endocrine-Related Cancer, a study involving the group of Prof. Albert Beckers at the University of Liège, Belgium described the case of a male to female transgender patient that developed breast cancer after 7 years of oestrogen and anti-androgen therapy.  The patient had to stop their hormone therapy and undergo surgery, but despite this, the cancer recurred and required chemotherapy.  Unbeknownst to the patient, multiple cousins had developed breast cancer and were found to have a mutation in the BRCA2 gene.

While the risks of cancer related to BRCA2 gene mutations have focused mainly on women, male mutation carriers are at greatly increased risk of male breast cancer and BRCA2 appears to act as a risk factor for prostate cancer, another hormone related tumor.  Indeed multiple members of the family also had developed prostate cancer.

“This very difficult case highlights two important points.”, said Dr. Vinciane Corman a lead author of the study. “Firstly, the awareness of family cancer risk due to BRCA2 gene mutations needs to involve both males and females, and families need to be thoroughly informed.  Information about a major risk factor like a BRCA2 mutation can lead to better decision making by potential carriers”.

She continued, “Secondly, the current cancer screening guidelines for BRCA2 mutation carriers have been written with the typical (or cisgendered) population in mind.  Due to greater openness about discussing transgendered individuals, future iterations of these guidelines might need to consider how best to manage these rare but difficult cases of BRCA2 mutation carriers that are considering being treated with cross sex hormones.”

World Health Day: Beat Diabetes

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There are currently 422 million people in the world who have diabetes – about 0.6% of the world’s population.

This figure is expected to double in the next 20 years.

In light of this alarming trend, the World Health Organization is dedicating 2016 World Health Day: Beat Diabetes to raising awareness of this life-threatening condition. Here are the basic stats:

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Diabetes is an endocrine disease. So, to mark World Health Day, we have created a collection of recent, high-impact diabetes articles and made them all free to read – for the next two weeks. So have a browse below and find out how science is bringing the fight to diabetes!

Journal of Endocrinology:

Current understanding of metformin effect on the control of hyperglycemia in diabetes Hongying An & Ling He.

Lack of glucagon receptor signaling and its implications beyond glucose homeostasis Maureen J Charron and Patricia M Vuguin.

Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice Linda Ahlkvist et al.

Identification of ABCC8 as a contributory gene to impaired early-phase insulin secretion in NZO mice Sofianos Andrikopoulos et al.

Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice Saeed Alshahrani et al.

 

Journal of Molecular Endocrinology:

Oxidative and endoplasmic reticulum stress in β-cell dysfunction in diabetes Sumaira Z Hasnain, Johannes B Prins and Michael A McGuckin.

Non-coding genome functions in diabetes Inês Cebola and Lorenzo Pasquali.

miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate gestational diabetes mellitus Yang Mi et al.

Inhibition of 11β-HSD1 by LG13 improves glucose metabolism in type 2 diabetic mice Leping Zhao et al.

Demethylation of the MafB promoter in a compromised β-cell model Wataru Nishimura et al.

 

Endocrine Connections:

Update on strategies limiting iatrogenic hypoglycemia Aldo Bonaventura, Fabrizio Montecucco and Franco Dallegri.

Central and peripheral pathogenetic forms of type 2 diabetes: a proof-of-concept study Dmitry M Davydov and Malik K Nurbekov.

Lower fasting blood glucose in neurofibromatosis type 1 Aline Stangherlin Martins et al.

Gut microbiota and diet in patients with different glucose tolerance Lilit Egshatyan et al.

Mendelian randomization studies of biomarkers and type 2 diabetes Ali Abbasi.

 

 Endocrinology, Diabetes & Metabolism Case Reports:

A silent myocardial infarction in the diabetes outpatient clinic: case report and review of the literature M S Draman et al.

Severe hypercalcemia and hypernatremia in a patient treated with canagliflozin Arshpreet Kaur and Stephen J Winters

Spontaneous diabetic myonecrosis: report of four cases from a tertiary care institute Soham Mukherjee et al.

One year remission of type 1 diabetes mellitus in a patient treated with sitagliptin Marcos M Lima-Martínez et al.

Suspension of basal insulin to avoid hypoglycemia in type 1 diabetes treated with insulin pump Mauro Boronat

World Health Day: Beat Diabetes

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There are currently 422 million people in the world who have diabetes. This figure is expected to double in the next 20 years. In light of this alarming trend, the World Health Organization is dedicating 2016 World Health Day: Beat Diabetes to raising awareness of this life-threatening condition.

For World Health Day we decided to raise awareness by asking two prominent diabetes experts about their work and the hurdles that they feel need to be overcome to beat this disease.

 

Dr Sof AndrikopoulosSof

Dr Sof Andrikopoulos is President of the Australian Diabetes Society and a Senior Research Fellow at the University of Melbourne. He is also Editor-in-Chief of two of our journals: Journal of Endocrinology and Journal of Molecular Endocrinology.

What is the focus of your current research?

My research strives to understand the genetic and biochemical mechanism(s) associated with beta cell dysfunction in type 2 diabetes. We recently identified a novel genetic cause for this dysfunction in a preclinical model (Andrikopoulos et al. J. Endocrinol 228:61-73, 2016).

How does your research have the potential to translate to a clinical setting?

While there has been a significant increase in drugs available to treat type 2 diabetes, none currently target beta cell dysfunction – the underlying cause of the disease. My group aims to address this.

Do you think the day will arrive when we’ll have beaten diabetes?

I truly believe that we will reach a point where we are able to effectively manage diabetes and avoid the associated life-threatening complications. This will be achieved by research focussed on understanding the genetic cause(s) of the disease.

What is the greatest highlight of your career so far?

My greatest achievement by far is to have mentored a number of scientists who are now forging their own independent careers in medical research.  Mentoring is the most important activity I engage in and I am extremely proud of all the scientists I have worked with.

 

Professor Nick Finer

Nick FinerAs a Consultant Endocrinologist at University College Hospital in London, Professor Nick Finer treats patients affected by diabetes and its complications. Here, Nick describes the progress that has been made during his career and his thoughts on the future of diabetes.

What have been the biggest advances in the field of diabetes in the last 20 years? 

Technologies such as glucometers, together with pen devices for insulin delivery, have allowed people with diabetes to achieve ever better glycaemic control. Cardiovascular risk management via statins has also had a huge impact on health improvement.

What are the biggest challenges you face in the treatment of diabetes?

Encouraging patients to understand that diabetes is never ‘mild’ and thus motivating them to reduce their personal health risks.

What do you feel needs to happen to enable us to beat diabetes?

We have to tackle the still growing devastation from ever-increasing obesity prevalence. Governments, societies and individuals have to reverse the unbridled proliferation of cheap, unhealthy food.

What is the greatest highlight of your career so far?

Seeing and being at the forefront of the transition of obesity from a curiosity to a cutting-edge scientific and clinical discipline.
To find out more about diabetes, visit You & Your Hormones, the official public information website of the Society for Endocrinology.

Patient Support Grant: How-To-Inject for adrenal crisis prevention

Every year, an average of around 30 people in England and Wales die from adrenal crisis, undertreated or undiagnosed Addison’s Disease*.

 Because of this the Addison’s Disease Self Help Group (ADSHG) teamed up with the Society for Endocrinology, which provided the kick-start funding for a how-to guide on giving an emergency hydrocortisone self-injection – an injection which could have saved some of those lives.

The aim was simple: to produce a series of short video clips which would give people with Addison’s – as well as their friends, family, school or work first-aiders – the knowledge and confidence to administer the injection correctly, using any of the available drug formulations. The charity was fortunate to have the close support and involvement of one of the UK’s leading adrenal specialists, Professor John Wass, who explains when it is necessary to give an emergency injection. You can find all videos on the ADSHG website. Below, watch when to give an emergency injection.

Above video: Adrenal crisis: when to give an emergency injection from Addisons Disease Self-Help Group video hub. Interview with Professor John Wass, Addison’s Clinical Advisory Panel Chair.

We hope that this education tool will not only save lives and reduce the length of hospital stays, but improve the confidence of those with Addison’s, helping them to maintain independence and overall quality of life. It pays to be prepared!

Patient Support Grant

Thanks to the Society for Endocrinology Patient Support Grant, funding was provided to begin the production of these life-saving videos. These grants assist small charities and patient support groups who work with endocrine-related conditions, and aim to fund projects directly benefitting patients.

The deadline for 2016 grant applications is now closed, but you can read more about the grant here, and start planning your application for 2017! We would love to hear from you in our quest to support patients.

Learn More

Watch all of the videos on the ADSHG website: How-To Guide: Addison’s Disease. They are also signposted on the ADSHG Facebook Page and Twitter feed.

*To learn more about Addison’s Disease, visit the Society website, You and Your Hormones.