In vitro studies of neutrophil regulation
Research type
Research Study
Full title
In vitro studies of neutrophil regulation
IRAS ID
242975
Contact name
Borko Amulic
Contact email
Sponsor organisation
University of Bristol
Duration of Study in the UK
8 years, 0 months, 0 days
Research summary
Neutrophils are the most common immune cells circulating in the blood stream: they account for 50-70% of all white blood cells and are essential for defending us from bacteria, fungi and other parasites. Neutrophils rapidly migrate to sites of infection to limit microbial proliferation by deploying toxic antimicrobial molecules that kill, disarm and contain pathogens.
The toxic antimicrobials carried by neutrophils must be carefully controlled because they also have the potential to damage our own tissues. Indeed, neutrophils are often incorrectly activated and cause pathology in many non-infectious diseases. These include various autoimmune diseases, such as lupus, rheumatoid arthritis and asthma, but also cancer and atherosclerosis.
Despite their relevance for health, we know very little about how neutrophils are regulated, making it difficult to design therapies for neutrophil-mediated diseases. The aim of this research is to understand which genes control neutrophil activity. To do this, we need to purify neutrophils from small volumes of blood from anonymous healthy donors. These neutrophils will be stimulated in vitro to understand which genes are activated. We will then test the involvement of these genes by inhibiting them in cultured cells. Since neutrophils are very short-lived, this can only be done in progenitors (blood stem cells). We will use progenitor cells from anonymised waste white blood cells from random normal blood donations and study neutrophils in the laboratory by culturing these cells with appropriate growth factors.
We will also purify neutrophils from small volumes of blood donated by anonymous patients with dysfunctional neutrophils due to immunodeficiencies, inflammatory disease or cancer. These samples will be from collaborations with studies that already have ethical approval. Comparing how neutrophils behave in healthy and diseased individuals will increase our understanding of neutrophil regulation and potentially lead to new therapies for neutrophil-mediated diseases.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
18/EE/0265
Date of REC Opinion
26 Oct 2018
REC opinion
Further Information Favourable Opinion