Role of the Small GTPase RhoG in Neutrophil Activation

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

When our lungs are invaded by viruses and bacteria, our immune system sends white blood cells to the site, which 'eat' and destroy the invaders. Unfortunately, the weapons that white blood cells use to kill bacteria can sometimes also damage our own lung tissue. This damage can cause diseases like Acute Respiratory Distress Syndrome (ARDS) and Bronchiectasis. At the moment, this process is not well understood and we have no strategies for preventing it. We have been studying a protein in the lungs, known as a small GTPase. We have genetic evidence that this protein has an important role in cells that are a major cause of ARDS. Mice that don't have the protein are perfectly able to fight infections from things like bacteria, but do not experience any associated lung damage. This suggests that this protein is involved in the process that damages lung tissue. This research aims to understand how our immune system attacks the lungs in this way. In so doing the researchers will make advances to prevent such damage. This grant from The British Lung Foundation is to determine whether this signalling mediator is potentially a good target for drugs to fight ARDS. Anti-inflammatory drugs available to treat lung disease are currently very non-specific, affecting many cell types and usually preventing the beneficial effects of white cells in fighting infection. Such drugs (e.g. corticosteroids) thus have many side effects including increased susceptibility to infection. By finding and understanding a new signaling pathway, we hope to identify possible drug targets that may limit inflammation without leading to increased risk of infection. This research may thus lead to novel treatments for ARDS and other inflammatory lung diseases.

Publications

10 25 50
 
Description This work changed our understanding of the molecualr mechanism by which neutrophil migration and reactive oxygen species (ROS, molecules used to kill pathogens) formation is coordinated. We found that a molecule called RhoG is a master regulator of migration and ROS formation through its ability to control a molecule already known to be a key player in neutrophils called Rac.
Exploitation Route This work has lead to a step advance in appreciation of the importance of RhoG and its role in many other areas of biology are now being investigated.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description This data has been used by the british Lung foundation to discuss potentialy new therapeutic targets to treat acute respiratory distress syndrome with pharamceutical companies.
First Year Of Impact 2010
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Invited lecturer to international meetings (average 2-3 per year) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact promoted discussions, collaborations

scientific collaborations, joint grants and publications
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019