X Close

UCL Translational Research Office Blog



Early Career Innovators: Correcting platelet defects in Wiskott Aldrich Syndrome (WAS), Cell & Gene Therapy TIN

By Alina Shrourou, on 16 June 2021

In this Cell & Gene Therapy TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Rajeev Rai highlights his Cell & Gene Therapy TIN Pilot Data Fund awarded project, involving hematopoietic stem cell gene editing to correct platelet defects in Wiskott Aldrich Syndrome (WAS).

What does your Cell & Gene Therapy TIN project involve?

Wiskott Aldrich Syndrome (WAS) is an X-linked recessive primary immunodeficiency disease characterised with severe, persistent, and life-threatening bleeding complications. This is caused by a genetic mutation in the WAS gene, which encodes a mutated WAS protein (WASp) leading to defective functional platelets. Without definitive treatment, the prognosis for this disease remains extremely poor. This is what my TIN funded project, which is titled “Correction of platelet defects in a Wiskott Aldrich Syndrome (WAS) humanized mouse model by hematopoietic stem cell gene editing”, aims to critically address.

We seek to investigate whether our recently established targeted genome editing platform could repair the mutated WAS gene and functionally correct platelet thrombocytopenia in humanised WAS mouse model. Our final goal is to translate this approach to human Haemopoietic Stem Cells (HSCs) harvested from WAS patients, which will be corrected ex vivo and re-infused intravenously following autologous transplantation protocols.

What is the motivation behind your project/therapeutic?

HSCs transplantation remains the definitive cure for WAS. However, lack of suitable matched donor accompanied by development of graft vs host disease has caused significant morbidities and mortalities. Although autologous HSCs gene therapy provides an attractive option, the use of lentivirus is associated with unregulated transgene expression and risk of insertional oncogenesis. Hence, a paramount urgency is required to develop an alternative yet safe gene correction strategy to cure WAS and associated platelet defects permanently.

Can you highlight any challenges have you experienced as an early career researcher in the cell and gene therapy/translational research space?

With a solid background in Immunology and Biochemistry, initial move into the field of cell and gene therapy was slightly challenging during the early stage of my research career. But having great mentors and colleagues in the department from whom I have learned enormous amount of molecular genomics and bioinformatics skills have tremendously aroused my interest in this field of translational  research.

Why did you want to apply to the Cell & Gene Therapy TIN Pilot Data Fund?

My previously completed project revealed the superiority of site-specific CRISPR/Cas9 editing over traditional gene therapy approach to rescue not just immune cells but also the defective WAS platelets in vitro (Rai et al., 2020). To extend such finding, I was planning to apply for various career development fellowship and larger grants. However, I realised I had to demonstrate some proof-of-concept in vivo translational data to support my hypothesis beforehand. And this is precisely what the Cell & Gene Therapy TIN Pilot Data Fund has helped me to do, and I would like to thank the UCL Translational Research Group for providing advice and immense support throughout the application process.

We are pleased to say that some form of TIN funding for the Cell & Gene Therapy TIN will be available this year in 2021. Please sign up to our newsletter to keep up with upcoming opportunities.

How did you find the process for the TIN Pilot Data Fund?

I thoroughly enjoyed the application process from start to finish including the dragon den pitching event, in which the ACCELERATE pitch training workshop helped me to prepare.

Sign up to the current open ACCELERATE training opportunity – ACCELERATE Potential, an online, self-paced translational training programme to help you learn the basics in translational research. 

What do you hope to achieve in the 6 months duration of your project?

The wealth of data generated from this TIN funding will define for the very first time the optimum fraction of gene edited HSCs required to functionally correct WAS platelet defect in a humanised mouse model without any side effects. This would enable the project to be more attractive to major translational follow-on funding and to industry engagement.

Dr Rajeev Rai

About Dr Rajeev Rai

Dr Rajeev Rai is a research fellow in UCL GOS Institute of Child Health.

His primary research lies in the development and application of novel gene editing and gene therapy technologies for the treatment of various haematological disorders.

Early Career Innovators: AAV Delivery in Dravet Syndrome, Cell & Gene Therapy TIN

By Alina Shrourou, on 16 June 2021

In this Cell & Gene Therapy TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Juan Antinao Diaz highlights his Cell & Gene Therapy TIN Pilot Data Fund awarded project, involving AAV delivery in Dravet syndrome.

What is the title of your project and what does it involve?

This project is called “AAV delivery of an NaV1.1 activator for the treatment of a Dravet Syndrome mouse model”. Dravet syndrome is a childhood epilepsy, caused by a mutation in one of the two copies of the SCN1A gene, which encodes the NaV1.1 ion channel. This results in a diminished expression of the protein, leading to the symptoms observed in patients. This project attempts to use a small molecule to enhance the function of the remaining NaV1.1 channels in a mouse model of Dravet Syndrome to hopefully alleviate the disease phenotype. To deliver the small molecule, we are using an Adeno-Associated viral (AAV) vector.

What is the motivation behind your project/therapeutic?

Dravet syndrome currently has limited treatment options, which struggle to control prolonged seizures and other comorbidities such as developmental delay. Patients with Dravet Syndrome unfortunately have an 15-20% mortality rate due to Sudden Unexpected Death in Epilepsy (SUDEP). In this project we aim to deliver a small molecule to enhance the function of NaV1.1 by using a AAV viral vector. As a proof-of-concept study we will aim to test this pre-clinical treatment in a mouse model of Dravet Syndrome, which also has a mutation in one of the two copies of Scn1a gene. If successful it could potentially offer an alternative treatment for Dravet Syndrome patients.

Can you highlight any challenges have you experienced as an early career researcher in the cell and gene therapy/translational research space?

I am currently in my first post-doctoral position. I would say the biggest challenge is the need to find funding for future projects. Although I was aware of this before, having to actually do it is a completely new “skill” on its own. Having no major track record has been a problem as most funding schemes require some history in the field to be eligible to apply, something that I currently do not have.

Why did you want to apply to the Cell & Gene Therapy TIN Pilot Data Fund?

This project is an exciting opportunity for me, as it is an idea I have had for some time, but could not figure out how to test it. If the results are promising, it will allow me to continue this work, applying to bigger grants, which otherwise I would have not been able to do, as these grants usually require preliminary data that for me as an ECR would have been difficult to generate without funding. The Cell and Gene Therapy TIN has given me the opportunity to kick-start this path.

Join the Cell & Gene Therapy TIN to keep up with upcoming funding opportunities. 

How did you find the process for the TIN Pilot Data Fund? What did you learn?

The process was simple. The application form was only a few pages long, mainly asking for details about the idea and how I was planning on executing it. I got the chance to participate in an ACCELERATE training session, which was extremely helpful when I had to present my project to the committee reviewing the applications. The suggestions I received from the coach have also been useful in other aspects, like explaining my research in terms that are easier to understand to an audience that is not familiar to the field I work in.

ACCELERATE’s online, self-paced translational training programme, ACCELERATE Potential, is now open for completion, to all. Learn more and sign-up.

What do you hope to achieve in the 6 months duration of your project?

During this time, I hope to generate preliminary data, mainly asking if the approach I proposed would be feasible as a possible treatment for Dravet Syndrome. I will test my vector in a mouse model of the disease and if the treatment modifies the symptoms, that data will become the basis on which I could apply for a bigger funding to continue this work. The timeline has been modified by COVID-19, but I am currently starting to produce the vector and hopefully I will start treating the first mice in the next few months.

About Dr Juan Antinao Diaz

Juan headsh

Dr Juan Antinao Diaz is a Research Fellow in the Maternal and Fetal Medicine department at the UCL EGA Institute for Women’s Health.

He completed his PhD at UCL in September 2020 and continued his work in UCL as a research fellow since then.

He is currently researching the use of a gene therapy vector in Dravet Syndrome.

Early Career Innovators: Novel Gene Therapy for Obesity, Cell & Gene Therapy TIN

By Alina Shrourou, on 27 May 2021

In this Cell & Gene Therapy TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Giulia Massaro highlights her Repurposing TIN Pilot Data Fund awarded project, involving the use of chemokines as a novel target to improve peripheral nerve regeneration.

What is the title of your project and what does it involve?

I am currently working on a project entitled: ‘Developing a novel gene therapy approach for the treatment of obesity’. This preclinical study proposes to design and test a gene therapy product that could provide an effective treatment for a disease that is a growing burden in society. The study will use viral vectors to deliver therapeutic genes to mouse models of obesity.

What is the motivation behind your project/therapeutic?

A large medical need exists for novel obesity treatments as rates continue to increase to worldwide epidemic status, with demonstrated association to cardiovascular diseases, diabetes, cancer and other disabling disorders. In the absence of a specific pharmacological treatment, lifestyle modification and bariatric surgery are the standard of care. However, this requires full participation of the parents in the case of children, and failure to maintain weight loss after intervention is often reported.

The development of a long-lasting gene therapy treatment will not only have a positive economic impact on the health system, but also impact personal and social aspects of morbid obese patients particularly for children and teenagers.

Can you highlight any challenges have you experienced as an early career researcher in the cell and gene therapy/translational research space?

I think it is not always easy to find your voice as a young researcher in such a crowded space as within science. In particular in a cutting-edge field like gene therapy, where the race to the next ground-breaking innovation or commercialisation is relentless, ECRs are often left behind. Personally, I have been incredibly lucky to be mentored by Prof Rahim and Prof Waddington, who supported my research, gave me the opportunity to present our work at a range of international conferences and involved me in different collaborations.

Giulia lab

Why did you want to apply to the Cell & Gene Therapy TIN Pilot Data Fund? How has it helped you?

The TIN Fund is a great opportunity for an ECR to build a preliminary data package that can be used in future applications for grants and fellowships. This first step in gaining independence is essential to grow further as a researcher in the academic environment, allowing you to strengthen the personal and professional skills necessary to build a future career as successful principal investigator within the University.

Learn more about the support provided through the TINs

How did you find the process for the TIN Pilot Data Fund? What did you learn?

It was fun! I enjoyed the ‘Dragons’ Den’ format, with both academic and industry panellists. I also attended the ACCELERATE workshop led by Simon Cane, who gave us great tips on how to present our work in the 3 minutes interview. Plus, I got the chance to meet other ECRs working in different fields and hear about their research – keep it up guys!

Future applicants will also be offered this training. Learn more – Translational training from UCL ACCELERATE

What do you hope to achieve in the 6 months duration of your project?

My plan is to develop vectors and test these in models of the disease. The COVID-19 pandemic has obviously slowed down my research, particularly affecting the availability of consumables and limiting the access to the Biological Service Unit. Nevertheless, so far I have managed to test in vitro some vector candidates, with encouraging results. I am currently producing large scale vector batches that will be used in the future in vivo studies.

Gene therapy, with its possible long-lasting effects on weight management, has to potential to offer a unified single-treatment strategy for the obese patient population, including cases due to genetic, environmental and/or behavioural factors.

About Dr Giulia Massaro

Giulia headshot

Dr Giulia Massaro is a NIHR GOSH BRC Research Fellow in Translational AAV Technology at the UCL School of Pharmacy. After her MRes in Functional Genomics at the University of Trieste and the International Centre for Genetic Engineering and Biotechnology, she joined Prof. Ahad Rahim’s Lab at UCL to complete her PhD in Gene Therapy working on rare paediatric diseases of infants. Since 2013 she has been involved in many translational gene therapy projects, collaborating with both academia and industry, focusing on rare neurological disorders with unmet medical need.

In 2020 Dr Massaro opened the GTxNeuro Viral Synthesis Facility, a state-of-the-art vector production laboratory for research-grade viral vector batches, where she provides expertise and support for new and established researchers wishing to produce customised viral vectors.

Early Career Innovators: Enhancing Stathmin-2 protein in Neurodegenerative Diseases, Small Molecules TIN

By Alina Shrourou, on 5 January 2021

In the next Small Molecules TIN interview as part of the Early Career Innovators series, acknowledging the amazing translational work being done by early career researchers within the UCL Therapeutic Innovation Networks (TINs), Benedikt Hölbling highlights his Small Molecules TIN Pilot Data Fund awarded project, “Enhancing Stathmin-2 protein levels in familial and sporadic ALS/FTD”.

What is the title of your project and what does it involve?

The title of my project is “Enhancing Stathmin-2 protein levels in familial and sporadic ALS/FTD”: Cellular loss of the protein Stathmin-2 is a common hallmark of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), two devastating neurodegenerative diseases. We aim to identify ways to modulate Stathmin-2 protein levels in cells to improve neuronal health. For this aim, we developed a high throughput screen to identify small molecules that could be used as novel therapeutics for ALS/FTD treatment.

What is the motivation behind your project/therapeutic?

ALS and FTD are fatal neurodegenerative diseases with no effective treatment available yet.
ALS, also commonly known as motor neuron disease, occurs when specialized motor neurons in the brain and spinal cord perish. Every year approximately 1700 people in the UK are newly diagnosed with this disease, with a mortality rate of 50% within the first 2 years.

Approximately 16,000 patients in the UK live with FTD. This rare form of dementia causes symptoms such as changes to personality and/or difficulties with language.

The majority of therapeutics under development would require regular, invasive lumbar punctures to administer or focus on specific disease-causing genes. However, most ALS cases are sporadic (90%) without familial history of the disease. Further, the genetic causes are very diverse. A common characteristic that is shared among most familial and sporadic cases is the loss of cellular Stathmin-2 protein levels. It was shown that overexpression of Stathmin-2 improves neuronal health in cell cultures (Klim et al., 2019 and Melamed et al., 2019). Therefore, finding modulators of Stathmin-2 expression may enable treatment of a large number of patients with various ALS and FTD disease backgrounds rather than targeting specific disease-causing genes. In addition, an oral delivery of small molecules is non-invasive and easy to administer.neurons ALS/FTD

Why did you want to apply to the Small Molecules TIN Pilot Data Fund?

We have developed a high-throughput screen in close collaboration with the Alzheimer´s Research UK Drug Discovery Institute at UCL. The Small Molecules TIN Pilot Data Fund will now enable us to perform two pilot screens with this model. Thereby, we will further increase the accuracy and reliability of our assay for large-scale screens in the future.

Furthermore, I applied for my personal development: There are very limited opportunities to apply for funding as an Early Career Researcher. Therefore, I was highly excited to be able to apply for the Small Molecules TIN Pilot Data Fund. From the start of this project, I could improve many of my skills in the lab and outside.

Join the Small Molecules Therapeutic Innovation Network

How did you find the process for the TIN Pilot Data Fund? What did you learn?

It was very exciting! I was never involved in a grant application before, so everything was very new to me. During the process, I attended two ACCELERATE training workshops. In the first one, I learned how to write more precise whilst not too scientific for my written application. Especially as a non-native speaker, this also will be a great help for future applications. However, the pitch was the most exciting part of the process. Explaining the innovation and importance of your project in only 2 minutes is very challenging and the ACCELERATE workshop was extremely helpful to set the right focus.

What do you hope to achieve in the 6 months duration of your project?

In the next months, we will perform two pilot screens with different small molecule libraries. Thereby, we will hopefully identify helpful tool compounds. Further, this helps us to optimize and validate our assay before utilizing larger small-molecule libraries in the future.

What are your next steps from now?

The next step is to perform two pilot screens together with the ARUK Drug Discovery Institute at UCL. Once we identify promising molecules with the screen, we will closely characterize them to determine which one of them is the most promising candidate for a novel ALS/FTD therapy.

About Benedikt Hölbling

Benedikt Hölbling works in Professor Adrian Isaac’s lab at the UK Dementia Research Institute at UCL.

He examines mechanisms of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) on the basis of stem cell models.

Investigating Plasma Exchange as a Treatment of Severe COVID-19 Infection

By Alina Shrourou, on 29 October 2020

Professor Marie Scully is a professor of haemostasis and thrombosis at UCL and a Consultant Haematologist working in non-malignant haematology at UCLH. Professor Scully has recently received a grant of around £360,000 grant from LifeArc for a phase 2 study to investigate the impact of COVID-19 on thrombosis and a potential mitigation therapy through plasma exchange.

What changes does COVID-19 cause in the blood and what does this mean for patients?

COVID-19 is a relatively new disorder that we knew very little about. Information that we had from severely affected countries like China and Italy was given to us in real time, and it became quickly evident that patients with severe symptoms showed two main effects: Inflammation, a reactive process, and thrombosis, a clotting process. As my main area of specialisation is in platelet disorders, immune conditions and in particular a very rare condition called thrombotic thrombocytopenic purpura (TTP), by background, in conjunction with our ICU colleagues, we were in a position to undertake and understand both of those two pathways in relation to COVID-19.

We had to spend time looking at all the thrombotic potentials and factors. Initially, it was thought that there were many blood clotting factors affected, however we were able to quickly disprove this internally because of the wealth of patients we had. What we noticed, was that all the blood clotting factors are essentially normal other than it would appear, one of them – von Willebrand factor (VWF), one of the biggest proteins in our body. These were found to be very high, which we would expect in patients who are severely unwell.

One of the specific factors that we look at in our disease area of TTP is something called ADAMTS13, an enzyme which is important in slicing up and controlling von Willebrand factor. This is crucial in ensuring that when we bleed, we have enough von Willebrand factor at the right length with platelets to stem bleeding in our body, but conversely if the VWF levels are very high and you have long types of the protein, it increases thrombotic risks. We were able to demonstrate in patients with severe COVID, that their VWF and ADAMTS13 levels were disproportionate, so that we were getting a very high ratio.

Furthermore, there were other groups that undertook histopathology and they demonstrated in patients who died from severe COVID, there was evidence of small clots in the blood vessels particularly in the lungs. It was thought that is, in conjunction with the increased thrombotic tendency, was highly significant and contributory.

Later, there was also a suggestion that other organs are affected, including the kidneys, brain and heart. It was on the basis of the inflammatory and thrombotic risk in severe COVID-19 patients, that we undertook a feasibility study to see the role of plasma exchange.

What is plasma exchange and what does the process involve?

Plasma exchange is an intervention that we primarily undertake in extremely sick patients. For us, it’s often in TTP, but it is used in many other areas of medicine. Plasma exchange is a procedure using a machine not dissimilar to a dialysis type machine, where the patient’s blood is removed from their body and the plasma, the straw coloured part of the blood, is taken away and the red cells and platelets are put back in. We then replace plasma with that collected from healthy, non-COVID donors. Patients don’t normally become unwell during this procedure as such, as there is no change in the fluid levels. Risks from it are that you can have reaction to the plasma, but this is extremely low risk given the type of plasma we use in the UK – we use specially treated plasma which prevents reactions and is very protective from viruses and other pathogens.

Why have you identified plasma exchange as a suitable therapeutic option to explore for COVID-19?

We undertook a feasibility exercise, to identify in those patients who had very severe lung injury who were on CPAP, or looked like they may need to be put onto a ventilator because their disease was so progressive. We undertook a daily   plasma exchange for 5 days. This involved the removal of a patient’s blood volume.

During this 5 day period, we were able to demonstrate that we could reduce the inflammatory component of COVID-19, which was very important because the inflammation was a continuous process that causes ongoing damage to organ tissue, which requires lessening in order for patients to start to improve. It reduced the thrombotic component of COVID-19 and we were able to bring van Willebrand Factor and ADAMTS 13 levels from very high levels down to normal levels – and that’s only over a five day course.

We also demonstrated that the patient’s respiratory function improved significantly over the five days in comparison to patients that were on intensive care at the time. We were also able to increase the understanding with regards to other organ involvement which was less clear at that time, for our patients that received plasma exchange, all of them had completely steady renal function. In the patients comparably on the intensive care unit that did not have plasma exchange, their renal function deteriorated and some required kidney support via dialysis. Therefore, we were able to show that we were protecting and improving not only the respiratory system, but also other organs, and that was by reducing the inflammatory and thrombotic component of COVID-19 – the effect of the virus hyper stimulating cells.

Please provide an overview of the work you are doing at UCLH for this LifeArc funded project.

The feasibility study was important in demonstrating the benefit of plasma exchange, especially so as plasma exchange is a very expensive and intensive therapy to consider without sufficient data to support its benefit. The data provided from our feasibility study was reviewed by LifeArc, who have supported a phase 2 study.

It is very important, in particularly in a very severe disease like COVID-19, to be able to demonstrate that a therapy is better or comparable in a randomized study to standard of care; we must demonstrate significant efficacy. LifeArc is funding this work through the phase 2 study, where we will investigate the role of plasma exchange compared to not having the treatment, in patients who have severe COVID-19. If we are able to demonstrate benefit of patient outcomes and prevent the need for ventilation and end organ damage, this can be published and replicated by any site in any country.

How will you access appropriate patients for this study?

We are looking at patients with severe COVID-19, which is  a very select group of patients who require hospital admission and organ support, primarily the lungs, which may include intubation and ventilation.

Patients must fulfil a certain level of what we call inclusion criteria, which are parameters they have to meet before we can offer them the opportunity to go into the study. This includes being aged between 18-70 and having specific levels of respiratory function.

The review of patients with COVID-19 that would be appropriate for our clinical trials is undertaken on a daily basis at UCLH, so we can identify in real time patients with COVID-19, the disease severity, and we can monitor that and if they meet the criteria, they will be offered access to this clinical study.

How have UCL TRO supported you in this project?

Initially on the back of the feasibility study, we were put in contact with the Translational Research Office (TRO), which is not an area of UCL that I had been familiar with. It was an absolute pleasure to work with Dr Pamela Tranter (Head, Translational Research Group) from the Translational Research Office, who made sure that the project was documented to cover everybody’s needs including the reviewer’s. The whole process really was very straight forward, in regards to accepting the work we had done and the benefit of the work, to supporting the funding application and liaising with LifeArc to see if they would be interested in funding the phase two study. Given that there was likely to be a phase 2 study to directly impact the UK, the time pressure was acknowledged by all, making the process very quick, both with the TRO and with LifeArc who asked the right questions and reviewed the protocol. It was a very fluid and receptive process, and the response we got with regards to funding the phase 2 was really an exceptional award.

Contact the UCL Translational Research Office

What are the next steps for your work?

Now that the study is open and available nationally to whoever wants to take part, I’m eager to complete the study in a very timely manner. This will of course depend on the number of patients that come through but we are pleased to have now started treating patients.

About Professor Marie Scully

Professor Marie Scully

Professor Marie Scully is a Consultant Haematologist at University College London Hospitals (UCLH) and Professor of haemostasis and thrombosis at UCL. Professor Scully’s particular area of interest is acquired haemostasis and platelet disorders, specifically Immune Thrombocytopenic Purpura (ITP).

Professor Scully runs specialist ITP and TTP clinics and works on obstetric haematology, as part of a team that specialises in treating varied and complex thrombosis, acquired and inherited bleeding disorders.

Early Career Innovators: Blocking LRG1 in Pancreatic Cancer, Biologics TIN

By Alina Shrourou, on 23 October 2020

In the next interview as part of the Early Career Innovators series, acknowledging the amazing translational work being done by early career researchers within the UCL Therapeutic Innovation Networks, Dr Athina Dritsoula and Dr Carlotta Camilli highlight their joint Biologics TIN Pilot Data Fund awarded project focusing on the effect of LRG1 blockade in pancreatic cancer.

How did this joint project come about?

CC: Athina and I both arrived at the Institute of Ophthalmology to do our post-docs where, weirdly enough, we don’t do eye-related research but explore vessel behaviour using ex-vivo models of angiogenesis and in vivo models of solid tumours.

What is the title of your project and what does it involve?

AD: The interest of our lab is focused on the LRG1 protein, which is involved in pathological angiogenesis, but we don’t know much about its normal function. Based on our research, we believe that blocking the function of the LRG1 protein by using a specific monoclonal antibody that we have developed in the lab will be beneficial in conditions with abnormal angiogenesis like cancer. In fact, LRG1 is upregulated in pancreatic cancer, which is a type of cancer with minimal survival that remains untreated. So, Carlotta and I designed this project to study the effect of LRG1 blockade in pancreatic cancer.

What is the motivation behind your project/therapeutic?

CC: Pancreatic cancer is a leading cause of deaths from cancer that kills about half a million people worldwide each year. The current standard of care involves combination cytotoxic chemotherapy, which often fails due to the complex tumour microenvironment. So, there is a great need for developing novel therapeutic strategies that will target new molecules and pathways, and we believe that our anti-LRG1 antibody could be a great novel therapeutic candidate.

Why did you want to apply to the Biologics TIN Pilot Data Fund?

AD: We both thought that the Biologics TIN Programme is a great opportunity to get enough funding to support a short 6-month project that would allow us to a) test our hypothesis and b) generate pilot data to design a bigger project in future if (a) proves right.

Join the Biologics TIN

What do you hope to achieve in the 6 months duration of your project?

CC: Well, we hope that we will manage to prove that our hypothesis is correct, and COVID-19 situation allowing, generate data to apply for more funding and get this project further. Our -very ambitious – aim is to get our antibody into clinical trials for pancreatic cancer in a few years’ time!

What are your next steps from now?

AD: Hope that our orders will be delivered on time and that our experiments will work as planned! We need to complete the project before a second lock down crushes.

Do you have any top-tips for applicants currently going through the application process for the other TIN Pilot Data Funds?

AD: The 10 minutes Dragons’ Den round felt much longer than it was! Be well prepared for all types of questions, and maybe have a mock interview with your PI, if possible.

CC: Spend enough time to prepare the slide presentation. It might seem easy but it’s not, as it needs to be very concise and straight forward!

About Dr Athina DritsoulaDr Athina Dritsoula

Dr Dritsoula studied an undergraduate degree in Molecular Biology and Genetics in Greece over a decade ago before arriving in the UK for a Master’s and PhD, and UCL has been home to Dr Dritsoula since. Although human genetics was Dr Dritsoula’s first love, Dr Dritsoula quickly found her “forte” in vascular biology – studying the biology of big human vessels during a PhD, and then smaller vessels stability and angiogenesis during post-doc.

About Dr Carlotta CamilliDr Carlotta Camilli

After completing a Master’s in Medical Biotechnology, Dr Camilli left Italy to start a PhD at UCL focusing on the use of vascular progenitors for the development of a bioengineered muscle.

However, Dr Camilli’s broad interest in translational medicine pushed her to explore a different pathological context during post-doc, namely the tumour angiogenesis. Dr Camilli found jumping on this new field a difficult but exciting challenge!

Early Career Innovators: A Biologics Therapeutic Target for Huntington’s Disease, Biologics TIN

By Alina Shrourou, on 7 October 2020

In the second interview as part of the new Early Career Innovators series, acknowledging the amazing translational work being done by early career researchers within the UCL Therapeutic Innovation Networks, Dr Anais Cassaignau highlights her Biologics TIN Pilot Data Fund awarded project “Developing an scFv binder against nascent huntingtin” and presents some advice for future applicants.

Please provide an overview of your Biologics project.

This project entitled “Developing an scFv binder against nascent huntingtin” is looking to exploit the unique features of nascent proteins, i.e. the shapes they form while they are being made. I am currently pursuing the novel disease angle that is the focus of this award.

Relative to the fully formed protein, the nascent protein is typically protected against misfolding /aggregation. We are looking to show that this entity may be a tractable therapeutic target in Huntington’s Disease.

What is the motivation behind your project/therapeutic?

I am interested in understanding how proteins fold while they are being synthesised by the ribosome, and how the ribosome itself regulates and modulates this process1. The correct folding of proteins in the cell is vital to all forms of life, and scientists are increasingly recognising that many diseases bear protein misfolding hallmarks including devastating neurodegenerative illnesses, several cancers and also diabetes.

Huntington’s is a devastating neurodegenerative disease, designated as an incurable disease with only symptomatic treatment currently available, and which often involves invasive delivery e.g. via spinal chord injections.  This is despite seminal work in the field that underpins much of what we understand regarding the pathological underlying processes and in particular how the causative agent, huntingtin, forms aggregates. I hope to be part of devising new therapeutic strategies that involve targeting the mutant form of huntingtin at the earliest point of biosynthesis – an angle which has not previously been explored in this manner.

Why did you want to apply to the Biologics TIN Pilot Data Fund?

I wanted to initiate a crucially needed orthogonal extension to the research I have been undertaking; building upon the wealth of collective knowledge that the entire lab and myself have been building together over years about how proteins are made and how they fold, and applying these paradigms to develop relevant disease-related models.

What do you hope to achieve in the 6 months duration of your project?

I want to demonstrate that targeting a nascent protein is possible, through binding an antibody and scFv to a nascent huntingtin during biosynthesis and monitoring how this modulates the folding/misfolding outcomes for this protein.

What are your next steps from now?

Finessing of assays and the production of samples of the nascent huntingtin. The protein will be translationally-arrested (a “snapshot” of biosynthesis) and then we will test the interaction of our antibody and scFv to it, and see how this influences the fate of this aggregation-prone protein.

Do you have any top-tips for applicants currently going through the application process for the other TIN Pilot Data Funds?

I would strongly encourage prospective applicants to reach out to the members of their respective TIN as the first step; their expertise will help you to appropriately refine your initial ideas and define the key questions in order to apply. Finally… Make a list of all the things you don’t know and read about them one by one.

Join the UCL Therapeutic Innovation Networks

About Dr Anais Cassaignau

Anais Cassiagnau headshot

Dr Cassaignau became interested in protein folding on the ribosome during her final year of BSc Biochemistry at UCL. Following this, Dr Cassaignau initiated a project within the Research department of Structural and Molecular Biology and has not left since, undertaking a Wellcome Trust-funded PhD and postdoc with John Christodoulou.

1. How does the ribosome fold the proteome? Cassaignau, AME, et al Ann. Rev. Biochem, 2020, 89, 389-415.  https://www.annualreviews.org/doi/abs/10.1146/annurev-biochem-062917-012226 

Medical Devices Regulation (MDR) 2021 – Implications for the Devices Academic Community

By Alina Shrourou, on 9 September 2020

Following last week’s announcement from the MHRA regarding changes to the regulation for devices to be marketed in the UK, we asked Translational Research Manager Dr Simon Eaglestone, who has represented the UCL Translational Research Office in various discussions around the new Medical Devices Regulation (MDR) for 2021, to comment on the implications this has for the devices academic community and the support available at UCL to ensure compliance and accelerate translation of medical devices to the market.

What do the new Medical Device Regulations mean for device projects in academia?
From 1 January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) will take on the responsibilities for the UK medical devices and in vitro diagnostic medical devices market that are currently undertaken through the EU system (i.e. CE mark). The new product marking will be termed UK Conformity Assessed (UKCA), with the current Medical Devices Regulations 2002 (UK MDR 2002) continuing to have effect in Great Britain after the transition period.

CE marking will continue to be used and recognised until 30 June 2023, with medical device manufacturers in the UK having to prepare to satisfy the new EU Medical Device Regulation 2017/745 (MDR) to be fully implemented 26 May 2021. Even with this most recent announcement of how medical devices are to enter the market in Great Britain it remains clear that to market UK medical devices in the EU, manufacturers will have to satisfy the new MDR and gain CE mark certification. Whilst the MDR is written to provide clarity of regulatory requirements of economic operators and sponsors of clinical investigations, there has been confusion and uncertainty amid the academic community regarding what the MDR actually means for those investigators working in universities and partner healthcare institutes on early stage medical device projects.

What are the most significant changes in the Medical Device Regulations?
The MDR defines new obligations for manufacturing a medical device that include revised risk classification, requirements of safety and performance, clinical evidence and vigilance reporting. Arguably, the most pertinent change to affect the academic community relates to Annex I of the MDR (the General Safety and Performance requirements) and the increased needs for technical documentation and quality management systems (QMS).

Article 10 of the MDR states what manufacturers need to put in place as a minimum QMS. The QMS encompasses a defined series of processes to ensure the appropriate documentation of the entire life cycle of a medical device (including regulatory compliance, risk management, design & manufacturing, product information, usage, safety and impact). As referenced in the MDR, ISO 13485 is the recommended (but not compulsory) international standard for QMS, whereby an organization needs to demonstrate its ability to provide medical devices and related services that consistently meet customer needs and applicable regulatory requirements.

Reflecting their charitable status, universities do not generally ‘hold’ CE mark certification or place products on the market (i.e. do not act as economic operators). Successful translation of academic device projects is usually achieved by increasing asset value within the context of academic research until such time that a strategic exit is made, either by establishing a ‘spin out’ company or brokering a licensing deal with an established device manufacturer. Either of these external parties would then take on the responsibility of managing an ISO 13485-certified QMS to support their application for CE mark certification and market authority approval for the new medical device.

What should be the impending approach to quality management systems in academia?
Universities and associated healthcare institutes undertake domestic development of non-CE marked devices, or research on modified CE marked devices or those used out of intended function (i.e. ‘CE-broken’). Whilst effectively acting as the manufacturers of these early-stage devices, the implementation and maintenance of an ISO 13485-certified QMS is resource demanding and rarely undertaken by academic centres. However, there clearly is the pressing need for a change in research culture and practice that addresses the need for appropriate technical documentation in the early life cycle of medical devices.

The incoming MDR has prompted health institutions to migrate their existing QMS infrastructure from ISO 9001- to ISO 13485-certification. Health institution exemption (HIE) from MDR may be secured for manufacturing, modifying and using custom made devices ‘on a non-industrial scale’, within the same health institution (i.e. legal entity). However this ‘in house manufacturing’ demands appropriate QMS and documentation to ensure such products meet the relevant General Safety and Performance Requirements. Significantly, health institutions will be compelled to apply for exemption under the new MDR, thereby closing a potentially overused pathway for academic medical device research via partner health institutions.

Making academic medical device translational more successful
To promote medical device development and successful translation to market with enhanced patient benefit, there is growing support in the academic community for initiatives that will improve knowledge of regulatory requirements and present investigators with both pragmatic and the least onerous solutions to satisfy regulatory compliance in early-stage device projects and facilitate commercialisation.

Whilst the academic exit strategy described earlier negates the need for implementing a fully certified QMS, there is a compelling incentive for device researchers within universities to commit time, effort and resources to implementing a proportionate QMS for each medical device project. The ability to attract external investment to support the progression of a university’s domestic device to market is greatly enhanced by the existence of a balanced QMS and documentation developed throughout the entire project lifetime toward ‘CE-readiness’.

The future for UCL
Just as the Clinical Trials Directive of 2001 enhanced the conduct of clinical trials on medicinal products for market within the European Union, the incoming MDR has presented a motivation for enhancement to the culture and way in which UCL researchers undertake and ultimately improve the likelihood of successful translation of university medical device development.

Throughout 2020, UCL’s Translational Research Office (TRO), Institute of Healthcare Engineering (IHE) and Joint Research Office (JRO) have been working closely to develop standardised tools that will support investigators in keeping and updating device project records.

Over the coming months, the Devices & Diagnostics Therapeutic Innovation Network (D&D TIN) shall be hosting community events to enable investigators to access local resources (e.g. QMS & document templates) and implement solutions for centralised management of a university department/Sponsor device project portfolio. Whilst non-compliance with the QMS would not preclude their ongoing research activity, it would likely hamper investigators ability to progress at a later stage (e.g. refusal of Sponsorship for clinical investigation).

Watch this space for the Devices & Diagnostics TIN QMS workshop, scheduled to take place before the end of the year (date TBC). In the meantime, become part of the Devices & Diagnostics community at UCL by joining the Therapeutic Innovation Networks: a platform for UCL, partner Biomedical Research Centres (BRCs) and industry partners to connect, collaborate and share best practices to translate at pace. Any workshops relating to the new MDR will be communicated to the Devices & Diagnostics TIN community through Teams and via email before being announced more publicly.

Devices & Diagnostics TIN logoWhat is the Devices & Diagnostics Therapeutic Innovation Network (TIN)?
The Devices & Diagnostics TIN is one of 6 UCL Therapeutic Innovation Networks hosted by the UCL Translational Research Office, positioned around a specific modality rather than subject area, to encourage the formation of strategic multidisciplinary alliances to close the academic/clinical/patient/industry interface.

Additionally, the TINs aim to widen participation and remove barriers to translation by providing education and funding opportunities to basic and translational researchers from Early Career Researchers to PIs.

The Development of Gene Therapy for Infantile Neuroaxonal Dystrophy

By Alina Shrourou, on 14 May 2020

Dr Ahad Rahim is an Associate Professor of Translational Neuroscience and Associate Director of Research at the UCL School of Pharmacy. Dr Rahim’s group works on the development of novel therapies for neurodegenerative diseases and recently at the end of 2019, received an MRC DPFS grant of £654,904 to develop gene therapy for infantile neuroaxonal dystrophy (INAD).

Please provide an overview of infantile neuroaxonal dystrophy (INAD) and the need to develop a new therapy.

INAD is a devastating inherited neurodegenerative condition that affects children. It’s caused by mutations in a gene called PLA2G6 that encodes for an enzyme known as Phospholipase A2, which leads to neurodegeneration in the nervous system of patients accompanied by an inflammatory response. The downstream effect of that is cognitive decline and progressive motor disorder, which leads to death in the first decade of life.

The symptoms usually present between 6 months and 3 years of age, and patients are completely dependent on family, carers and the healthcare system for the duration of their lives. This, of course, has a very significant emotional and social burden.

Palliative care is currently the only way to respond to INAD, with there being no clinical treatment available for the condition. Therefore, there’s an overwhelming need to develop a new and effective therapy for INAD.

We work closely with Professor Manju Kurian at the UCL Great Ormond Street (GOS) Institute of Child Health and she is the clinical lead for patients with this disease. She sees patients living with the condition and is invaluable to our work. Professor Kurian and I have been working together for the last 4/5 years to provide proof of concept studies supportive of gene therapy for INAD.

Why have you identified gene therapy as a good treatment potential for INAD?

The theory of gene therapy has been around for quite a while but has taken almost a generation for it to develop into something that is clinical viable. UCL now proudly has many success stories of gene therapy clinical trials leading to spinout companies.

Visit the UCL Therapeutic Innovation Networks (UCL TINs) website for more gene therapy case studies.

So overall, we have a very good track record of gene therapy at UCL.

Gene therapy is revolutionising the way that we think about treating genetic diseases and although it has taken a while to get to this point, there have been some really pioneering clinical trials in neurological diseases similar to INAD. One example is spinal muscular atrophy where gene therapy has had life-saving effects. This success story in a neurological condition with gene therapy, have led us to investigate the use of gene therapy for other neurological diseases – INAD being one of them. We know which gene is defective in INAD, so we can investigate the use of gene therapy to deliver a healthy version of that gene to compensate for the defective version. We do this in the hope that this would cure the patient.

Therefore the three overwhelming considerations that make us think that INAD is a good candidate for gene therapy are: we know what the effected gene is, there is no other option available to the patient, and gene therapy has had a good effect in another genetic neurological condition.

What is AAV-mediated gene therapy?

Adeno-associated viruses (AAV) occur naturally; we have all been infected with AAV at some point and since they are non-pathogenic, you won’t even know you have it. AAV-mediated therapy involves delivering a gene for therapeutic purposes using a modified and safe AAV virus.

Getting genes into cells is not an easy task because our cells are designed with defensive mechanisms in place to prevent exogenous DNA from coming in and corrupting its own DNA. Therefore to be able to get your therapeutic gene into the right part of the cell that you want to correct, you need a vehicle or mechanism for it to get in – that’s where we use viruses like AAV.

Viruses are at the top of the food chain in terms of being able to deliver their genetic material into a cell. In order to exploit this ability for gene therapy, we take viruses like AAV, remove the bits which are potentially harmful, toxic or we don’t need, and we replace that with therapeutic genetic material – in the instance of INAD, it’s the PLA2G6 gene. We then use the virus as a trojan horse, as it now carries our therapeutic gene and delivers it into the cell effectively.

How will you optimise AAV9-mediated gene therapy for INAD as part of this DPFS project?

In mouse models, we have been able to show that AAV-9 gene therapy is effective by rescuing the mouse from premature death and reducing the loss of neurons in the brain. However, as always, there’s room for improvement in the vector. It is important to remember that due to size differences between a mouse brain and human brain, what you do in a mouse, is very different to what you do in a human being. What we want to do is give ourselves the best chance of therapeutic effect in that much bigger brain – and that is a challenge.

In this grant, we want to modify the AAV vector by improving elements of it. This includes the optimising how the gene is expressed once it’s delivered into the cell. We’re also looking at the best way of administering this AAV9 vector via different routes of administration to give the best coverage in a larger brain.

Can you describe the results from your proof-of-concept data that demonstrates therapeutic efficacy of this approach?

Over the past 4 years we’ve been working on a mouse model that has a mutation in the PLA2G6 gene. The model has very similar symptoms, levels of neurodegeneration and inflammatory response in the brain as human INAD patients do. This is important because what we don’t want to do, is study a mouse model that is not faithful to what happens in human beings. We have been able to confirm that that is a good model to be able to test future novel therapy on.

We then designed an AAV9 vector which carried the therapeutic human PLA2G6 gene and we administered this into the PLA2G6 deficient mice. We looked to see if there was an improvement in lifespan, locomotor function, behaviour and neuropathology.

We were pleased to find a significant improvement in all of the markers of therapeutic efficacy that we were looking for which showed benefit from the AAV9 gene therapy. That’s quite promising in such an aggressive model of neurodegeneration.

It was on the basis of that preliminary data that we applied to the MRC asking for funding to be able to take this further towards the clinic. If we make the AAV9 vector better, can we administer it in a way that is more efficacious and would be most beneficial one day in human beings?

What stage are you up to with your work?

Now that we have shown proof-of-concept in our work, we want to make further improvements on survival, locomotor function and neuropathology in the mice so that we develop the very best therapy in human beings and we know that there is room for improvement in the vector to achieve this.

The two year grant will allow us to do more preclinical studies – including large animal studies which will help give us a lot of information as to how it will work one day in humans.

Can you highlight any barriers to translation you have come across?

In the gene therapy community there are certain hurdles which exist as potential bottlenecks. As gene therapy is growing very quickly and is a massively expanding field, the availability of facilities to manufacture vectors for clinical use, is relatively few in number. They aren’t many places that can take a viral vector and produce it at the quantity, quality and purity that would be suitable to go into human beings.

If you think about the amount of gene therapy activity happening around the world – it’s a huge burden on those facilities, meaning that stakeholders are having to wait an extremely long time to get the vector manufactured at an acceptable grade which they can then use to run a clinical trial.

There needs to be more of these facilities and more people trained in gene therapy technology. I would say that we as academics, need to be training more people in gene therapy technology to provide the workforce for a field that is growing so quickly.

Another consideration is the business side of gene therapy. Sometimes there are patents on certain vectors or parts of a vector. This is a commercial necessity and you may need a license to use that particular technology. This is not a problem in itself, but is something else that we have to think ahead of when working in such a rapidly expanding field.

When you write MRC DPFS applications, there are very specific questions in the application around freedom to operate which UCLB were able to help us answer, including “What is the current IP issues around this?”, and “Do you foresee any problems in the future in terms of getting access commercially to these technologies?”. These are important questions to ask because the MRC want to be sure that whatever we are developing has a commercial exit strategy. It would be tragic if we develop a promising treatment but don’t have commercially viable routes to take it forward and get it to the number of patients that need it.

How has the UCL Translational Research Office (TRO) supported you in your work?

The TRO have helped a lot in many translational projects that have come out of my lab. I’ve worked with Translational Research Manager Dr Alethea Cope right from the beginning for every one of my projects, and she has been instrumental. Alethea has recently moved on from the TRO but I am fortunate to now have support from Dr Simon Eaglestone (UCL TRO Translational Research Manager) who has managed other gene therapy projects at GOS, which are now progressing to clinical trial.

These projects are often complex in the way that they are designed and lot of things that we’re doing are the first time anyone has tried them. Within our projects, it is a common need to contract out some of the work to contract research organisations (CRO’s) external to UCL.  This process requires a lot of time invested in terms of engaging with those CROs, making them understand what work we want to do, and getting quotes from them on very specialised/tailored work. Where the TRO have been really instrumental, is connecting me with the right CROs and allowing me to have that conversation with them.

The TRO are also very up to date and knowledgeable about what’s happening in general in the gene therapy field. They often know things that we don’t and so they are able to guide us in the right direction. For example, in the manufacturing of the clinical grade gene therapy vectors, the TRO know which facilities are perhaps in the best position to help us. Those nuggets of information are critical and are invaluable in helping us to succeed.

What are the next steps for this project?

Once this grant has ended, it will allow us to have more detailed conversations with the clinical community and with regulators who will assess our work and determine whether it’s safe for potential clinical translation. The link between my lab and clinicians like Professor Kurian is really important, and it will allow us to move along a well thought-out translational pathway and get this treatment to patients who badly need it.

About Dr Ahad RahimAhad Rahim

Dr Ahad Rahim is an Associate Professor in Translational Neuroscience and leads a research team at the UCL School of Pharmacy focussed on studying lethal or debilitating neurodegenerative disorders to evaluate disease mechanisms and develop novel therapies.

His team are involved in the pre-clinical testing of therapeutic modalities including gene and stem cell therapies, exosomes and small molecule neuroprotective drugs. Diseases and conditions being studied in Dr Rahim’s laboratory include Niemann-Pick disease type C, Gaucher disease, PLA2G6-associated infantile neuroaxonal dystrophy (INAD), Batten disease (CLN2, CLN3, CLN5, CLN6 and CLN7), Parkinson’s disease, neonatal hypoxic-ischemic encephalopathy and peripheral nerve damage.

UCL Spotlight on Dr Jane Kinghorn, Director of the Translational Research Office (TRO)

By Alina Shrourou, on 25 November 2019

In September, Dr Jane Kinghorn appeared in the Week@UCL Spotlight On feature and mentioned an upcoming event with initiatives to support early career researchers. Now that the invite for this event is out, we wanted to reshare the interview with more details about the event and how to register for the event taking place on 21st January 2020.

What is your role and what does it involve?

I can truly say that I have one of the most privileged positions in the University. As Director of the Translational Research Office (TRO), I get to work with the best scientific minds that conceive amazing solutions to some of the most devastating diseases and unmet medical needs of our time.

My role is to inform and deliver the strategy, organisational culture, capability and processes necessary to deliver the UCL and our three NIHR Biomedical Research Centre’s mission of “Accelerating translation for health and wealth”. The cornerstones of the strategy are 1) to nurture novel therapies, devices and diagnostics from across UCL and its partner hospitals into projects attractive for translational funding or further development with partners, 2) provide access to complementary capacity, expertise and skills in translational science 3) understand and address bottlenecks to accelerate translation 4) share knowledge of therapeutic translation across the career spectrum.

I am fortunate to lead a group of highly talented applied scientists within the TRO all with significant industry, biotech and academic research experience, who do all the hard work in helping this come to fruition.

How long have you been at UCL and what was your previous role?

I have been at UCL for just over 10 years. The TRO was formed with two other colleagues in 2010 and has since grown (through successful grant applications) to a team of 24.  Prior to UCL, I worked for 16 years in drug discovery roles at GlaxoSmithKline, providing strategic leadership on translational work and clinical research programmes leading multidisciplinary research teams working on neuro and inflammatory projects on multiple targets.

What working achievement or initiative are you most proud of?

I am most proud of my tremendous team who display daily a shared passion with our researchers and collaborators for advancing projects to make a real difference to patients.

Tell us about a project you are working on now which is top of your to-do list

Top of the list is encouraging engagement/participation in biomedical translation with our early career researchers (ECRs). Part of our strategy is to share knowledge and experience through our Therapeutic Innovation Networks (TINs) and to address education needs though our recently awarded Wellcome Trust Translational Partnership Award. The team are currently meeting with ECR’s to seek feedback on the new support currently being developed (pilot data scheme, educational courses and workshops/sandpits etc.). We will be highlighting this range of support at a launch event on Tuesday 21st January 2020. Please look out for details in the coming month.**Update November 2019 – We’re inviting all UCL researchers interested to know more about translation, particularly encouraging early career researchers, to celebrate the activities of the UCL/Wellcome Trust Translational Partnership Award with us. The event will include a launch event to announce the initiatives surrounding the UCL Therapeutic Innovation Networks (TINs), followed by a networking session and an opportunity to become familiar with the support available for translation at UCL. 

The event will be introduced by the inspirational Baroness Eliza Manningham-Buller, previous Director General of MI5 and since 2015, Chair of the Wellcome Trust. The agenda also includes talks from a number of Wellcome Trust-funded researchers, across a variety of disciplines, who will share their stories as translational case studies. Additionally, we will announce key dates for pilot funding schemes and translational training programmes.View the full agenda and register here.

What is your favourite album, film and novel?

That is difficult as I like what I’m listening to, reading or watching now so I have given two answers….

Album: Fleetwood Mac – Rumours and more recently Dua Lipa – Dua Lipa

Film: West Side Story and more recently Hidden Figures

Novel: Little Women – Louisa M Alcott and more recently The Unlikely Pilgrimage of Harold Fry – Rachel Joyce

What is your favourite joke (pre-watershed)?

I’m terrible at telling jokes but even I can get this one across…
“How do you make an octopus laugh?”
“With ten-tickles!”

Who would be your dream dinner guests?

Tom Kerridge to cook, Janice Robinson to select the wines, Elton John to provide the music with additional guests being Jonathan Agnew, Betty Boothroyd, Idris Elba, Peter Kay, Andy Murray and Darcey Bussell.  Quite a mix!

What advice would you give your younger self?

Time moves quickly so cherish every opportunity to spend it with friends and family

What would it surprise people to know about you?

I am a sports fanatic, playing and watching it. I play competitive hockey every weekend through the autumn and winter and am an avid Radio 5-Live as well as Test Match Special listener.

What is your favourite place?

I collect favourite places, therefore the last place I visited is my current favourite – Yellowstone National Park (see picture below).