Approved Research

Single cell resolved transcriptional profiling of blood in the UK Biobank

Lay summary

Human variation exists across a continuous spectrum, from physical attributes such as height to cognitive function and intelligence. While a significant proportion of this variation is influenced by the environment and external factors such as diet, there is a substantial component driven by our genes. In the extreme case the inheritance of a single faulty gene from our parents can lead to disease, for example in the case of cystic fibrosis or sickle cell anaemia. These are classed as monogenic disorders, where one faulty gene alone can lead to a dominant trait or disease. However, most variation is not driven through function of a single gene but rather the sum of many subtle changes in genes or regions that control gene activity. The unique combination of each person's millions of genetic variants contributes to the spectrum of 'multigenic' variation of human traits and diseases. Characterising the contribution of our genetic make-up to human variation represents a great challenge.

There are two main categories of immune cells circulating in the blood; innate and adaptive. The innate immune system represents the body's first line of defence to infection and acts very fast. On the other hand, the adaptive immune system reacts slower to infection but has the ability to build a memory of previous infections. Once these cells recognise an antigen like bacteria or viruses they can be neutralised. Vaccinations utilise this system and once antibodies have been produced the body can react quicker to the infection. However in some cases the immune system malfunctions resulting in autoimmune disease, where the body's own immune system attacks the joints as is the case for arthritis, or insulin producing cells within the pancreas in the case of diabetes. As such blood represents both an advantage as an exemplar system in which to study human variation and as a target for treatments to many important diseases.

In this project we aim to extract immune cells from blood donated by UK Biobank volunteers and subject them to a state of the art technique known as single cell RNA sequencing. RNA is produced when a gene is activated and by analysing the types and amounts of RNA produced in single immune cells we will be able to link this to the genetic variation between humans. It would give us a better understanding of various diseases and help with the development of new markers of early disease detection and treatment.