Beta cells

Tiny molecules with big potential for type 1

Dr Aida Martinez-Sanchez and Dr Prashant Srivastava’s Beta Cell Therapy Innovation Project Grant

Drs Prashant Srivastava and Aida Martinez-Sanchez

Led by Drs Aida Martinez-Sanchez and  Prashant Srivastava at Imperial College London, along with Dr Teresa Rodriguez-Calvo at Helmholtz Zentrum Munich, this project will investigate how tiny molecules called microRNAs change the function of insulin-making beta cells. Studying how these molecules are different between beta cells from people with and without type 1 diabetes, and in those grown from stem cells, could help to improve the effectiveness of beta cell transplants. 

Background to the research project – every beta cell is unique

In type 1 diabetes, insulin-producing beta cells are destroyed by the immune system. Beta cells are all unique, and some are more prone to the type 1 immune attack. This uniqueness is known as heterogeneity and plays an important role in how type 1 diabetes develops. 

MicroRNAs (miRNAs) are tiny molecules in our cells that switch different genes on and off and change how the cell works. They’re important in beta cell development and function, and differences in beta cell miRNA could be key to why some beta cells are more vulnerable to the type 1 attack. 

Drs Aida Martinez-Sanchez and Prashant Srivastava think that beta cells grown from stem cells – which are being developed as potential treatments for type 1 diabetes –   might have different miRNAs than beta cells found in humans. This could explain why stem cell-beta cells don’t function as well as human beta cells and are often rejected after transplantation if they’re not destroyed by the immune system first. They also suspect that there are differences between beta cell miRNA in people with and without type 1 diabetes. 

What will the team do in this project?

Drs Martinez-Sanchez and Srivastava want to examine differences in the miRNA of different kinds of beta cells. There are two main parts to the research: 

  1. In beta cell and pancreas samples from donors with and without type 1 diabetes, they’ll investigate which genes are switched off by miRNAs with a method called AgoTRIBE. This works by ‘tagging’ switched off genes in individual beta cells. They’ll also use an advanced microscope to look for the tags, helping them to find out more about miRNA and how it impacts beta cell function. 
  2.  Next, they’ll use AgoTRIBE to understand whether miRNA in beta cells grown from stem cells is different to that in beta cells from donors. They’ll also use a technique that will help them understand more about the role of miRNAs in beta cell survival and healthy functioning. 

How will this research help people with type 1 diabetes?

Understanding how miRNAs influence the behaviour and survival of beta cells could help scientists to develop healthier, longer-lasting lab grown beta cells. This could help to improve the effectiveness of beta cell transplants by making sure the transplanted cells are tougher and less likely to be rejected, which in turn would reduce the need for insulin injections.  

This research could also shed more light on how to protect beta cells from the immune attack, potentially preventing or slowing down the progression of type 1 diabetes.  

Dr Aida Martinez-Sanchez said:

“MicroRNAs are tiny molecules essential for keeping insulin-producing beta cells alive and well. However, not all beta cells are the same—some are more resistant to immune attack, while others are more vulnerable. Also, some beta cells are better at releasing insulin than others. In this project, we will use pioneering molecular and cellular biology techniques to explore whether microRNAs contribute to these differences.

“Identifying which miRNAs to manipulate could help us to grow the very best beta cells in the lab. The complex methodologies we’re developing have the potential to form the basis of future research in other important aspects of beta cell biology, such as how to reduce the risk of transplant rejection, or delay or prevent beta cell destruction in type 1 diabetes.”