Professor Sarah Richardson co-leads the Islet Biology Team at the University of Exeter Medical School. She has been researching diabetes since 2007 and is one of the Senior Research Fellows for the Type 1 Diabetes Grand Challenge. Her project will investigate how and why the immune system destroys insulin-producing beta cells in type 1 diabetes, and how the process may differ between people with the condition.

Are there different types of type 1 diabetes?

In her previous research, Sarah showed that the biological processes driving the development of type 1 diabetes are not the same in everyone with the condition and there are different subtypes of type 1 diabetes. She found that the number and type of immune cells that children with type 1 have are different to those present in people diagnosed in their teens or older. When people are diagnosed with type 1 at an older age, they have more beta cells than expected. Sarah thinks this is because some of their beta cells are dysfunctional rather than destroyed.

In this project, Sarah will study pancreas samples taken from people at the early stage of type 1 development to look at differences between people in how their immune system attacks and destroys beta cells. This research will allow the subtypes of type 1 to be better defined.

How will defining subtypes help people with type 1?

Knowing the form of type 1 an individual has could help tailor how their diabetes is treated and managed. Sarah’s previous research suggests that the effectiveness of immunotherapy drugs for type 1 will be dependent on their specific form of type 1 diabetes. Sarah hopes to learn more about which treatments might work best for different people by examining how immunotherapy drugs work in each form of type 1. With this knowledge, scientists will be able to work on creating an armoury of new treatments that target different lines of the immune system’s attack, so everyone affected by type 1 can be matched to the best treatment for them.

Understanding how beta cells defend themselves

Sarah will also explore how beta cells can fight back against the immune attack and why beta cells in some people with type 1 can survive for many years after their diagnosis. She will use pancreas samples from people with type 1 to explore how beta cells (and the pancreatic islets they are located within) defend themselves against the immune system. To do this, she will use state-of-the-art imaging equipment to look at the samples as well as growing systems of living beta cells and immune cells in the lab. Sarah will investigate a protective layer that surrounds beta cells, called the basement membrane, to understand more about when and how it develops. She’ll also identify molecules made by beta cells that can fortify them against the immune attack.

How will understanding how beta cells defend themselves help people with type 1?

It is hoped that these insights will be used to develop new treatments to shield beta cells from the immune system attack in type 1 diabetes. If combined with treatments to replace damaged and destroyed beta cells with healthy lab-grown versions or islets from organ donors, this could be a potential cure for type 1 diabetes

Professor Sarah Richardson said:

“As a scientist, one of the things that interests me about diabetes is the way it affects people in extremely different ways. My fellowship will explore how the early development of the pancreas may influence the form of type 1 diabetes a person develops. Ultimately, this will help us tailor existing and emerging therapies to the individual, maximising the benefits for people with type 1 diabetes.

“I also aim to develop a better understanding of how beta cells can protect themselves from the immune attack, which not only holds huge promise for improving beta cell replacement strategies but has the potential to bring us closer to a cure.”

Dr Victoria Salem is a Clinical Senior Lecturer in Diabetes and Endocrinology at Imperial College London. She researches the islets in the pancreas, which is where insulin-producing beta cells and other hormone-producing cells are located. The aim of her Grand Challenge project is to develop a device that can be implanted into people with type 1 diabetes to deliver a new supply of beta cells.

Shielding new beta cells from the immune attack

Finding an effective way to replace damaged and destroyed beta cells with healthy, functional beta cells is critical to curing type 1 diabetes. One way of making new beta cells is to grow them in a lab from stem cells, a type of cell which can develop into any other cell type. Trials are ongoing in the US to transplant these lab-grown beta cells into people with type 1. But these patients must take drugs called immunosuppressants (which can have serious side effects) to stop their immune systems attacking these new beta cells.

To overcome the need for immunosuppressants, Vicky plans to hide her lab-grown beta cells inside a soft, jelly-like case. Beta cells need an extensive blood supply to provide them with the oxygen and nutrients they need. So, Vicky needs to create a system that allows nutrients to get to the beta cells, but doesn’t let immune cells in. Once implanted into someone with type 1, this case would keep the precious beta cells safe from the immune system attack which caused their type 1 in the first place. This research could also help protect islets transplanted from organ donors, meaning transplant recipients wouldn’t need to take immunosuppressants.

How will Vicky create a safe haven for beta cells?

Vicky and her team will collaborate with researchers at the University of Birmingham to use specialised techniques to create clusters of beta cells from stem cells and find those which are good at releasing insulin.

The next step will be to enclose these beta cell clusters in a supportive water-based medium called a hydrogel. Vicky will work with world leading researchers to develop a hydrogel which can support the beta cells both physically and nutritionally. By experimenting with different materials, they will engineer a sophisticated device which keeps the supporting blood vessels close enough to nourish the beta cells but far enough to prevent immune cell invasion.

Once they are happy with the design, they will print the whole system of protective coating and beta cells in 3D using a high-tech machine called a bioprinter. Vicky said: “Imagine a colour inkjet printer – nozzles eject different coloured ink onto paper, line by line, to build up your document. The nozzles of our bioprinter variously contain our hydrogels and different living cells. We can even print the pattern of hydrogels and cells in precise three-dimensional structures.” She will then test the implant in mice to build the evidence needed to take it into clinical trials with people with type 1 diabetes.

How will this research help people with type 1?

It is hoped this research will lead to the development of a cell-based device which can be implanted into people with type 1 to help them to produce their own insulin again, potentially forming part of a cure for type 1. Within her five-year Fellowship, Vicky hopes her device will be ready to test in early clinical trials of people with type 1.

Dr Victoria Salem said:

“There are so many hurdles to creating a successful cell-transplant for people with type 1 diabetes. We can only crack this by working together – building fruitful collaborations across disciplines and the Grand Challenge is providing the boost we need to mobilise the best scientists in the UK towards this cause!

“I will lead a team of outstanding researchers, and international collaborators, to engineer improved beta cell replacement technologies.

“The dream for a cell-based cure for type 1 diabetes is now tantalisingly close – I’m so excited and honoured to be a part of this journey.”

Dr Victoria Salem is a Clinical Senior Lecturer in Diabetes and Endocrinology at Imperial College London. She researches the islets in the pancreas, which is where insulin-producing beta cells and other hormone-producing cells are located. The aim of her Grand Challenge project is to develop a device that can be implanted into people with type 1 diabetes to deliver a new supply of beta cells.

Shielding new beta cells from the immune attack

Finding an effective way to replace damaged and destroyed beta cells with healthy, functional beta cells is critical to curing type 1 diabetes. One way of making new beta cells is to grow them in a lab from stem cells, a type of cell which can develop into any other cell type. Trials are ongoing in the US to transplant these lab-grown beta cells into people with type 1. But these patients must take drugs called immunosuppressants (which can have serious side effects) to stop their immune systems attacking these new beta cells.

To overcome the need for immunosuppressants, Vicky plans to hide her lab-grown beta cells inside a soft, jelly-like case. Beta cells need an extensive blood supply to provide them with the oxygen and nutrients they need. So, Vicky needs to create a system that allows nutrients to get to the beta cells, but doesn’t let immune cells in. Once implanted into someone with type 1, this case would keep the precious beta cells safe from the immune system attack which caused their type 1 in the first place. This research could also help protect islets transplanted from organ donors, meaning transplant recipients wouldn’t need to take immunosuppressants.

How will Vicky create a safe haven for beta cells?

Vicky and her team will collaborate with researchers at the University of Birmingham to use specialised techniques to create clusters of beta cells from stem cells and find those which are good at releasing insulin.

The next step will be to enclose these beta cell clusters in a supportive water-based medium called a hydrogel. Vicky will work with world leading researchers to develop a hydrogel which can support the beta cells both physically and nutritionally. By experimenting with different materials, they will engineer a sophisticated device which keeps the supporting blood vessels close enough to nourish the beta cells but far enough to prevent immune cell invasion.

Once they are happy with the design, they will print the whole system of protective coating and beta cells in 3D using a high-tech machine called a bioprinter. Vicky said: “Imagine a colour inkjet printer – nozzles eject different coloured ink onto paper, line by line, to build up your document. The nozzles of our bioprinter variously contain our hydrogels and different living cells. We can even print the pattern of hydrogels and cells in precise three-dimensional structures.” She will then test the implant in mice to build the evidence needed to take it into clinical trials with people with type 1 diabetes.

How will this research help people with type 1?

It is hoped this research will lead to the development of a cell-based device which can be implanted into people with type 1 to help them to produce their own insulin again, potentially forming part of a cure for type 1. Within her five-year Fellowship, Vicky hopes her device will be ready to test in early clinical trials of people with type 1.

Dr Victoria Salem said:

“There are so many hurdles to creating a successful cell-transplant for people with type 1 diabetes. We can only crack this by working together – building fruitful collaborations across disciplines and the Grand Challenge is providing the boost we need to mobilise the best scientists in the UK towards this cause!

“I will lead a team of outstanding researchers, and international collaborators, to engineer improved beta cell replacement technologies.

“The dream for a cell-based cure for type 1 diabetes is now tantalisingly close – I’m so excited and honoured to be a part of this journey.”