GPR120: a G protein-coupled receptor with the potential to regulate insulin secretion and inflammation
Lead Research Organisation:
University of Glasgow
Department Name: College of Medical, Veterinary, Life Sci
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Planned Impact
The studies proposed in the current application plan to make fundamental progress in our understanding of the challenging topic of the physiological consequences of activation of the G protein-coupled receptor GPR120.
Who will benefit from this research and how will they benefit?
This receptor is attracting considerable interest as a potential novel therapeutic target at the interface between inflammation and chronic metabolic disease. However, despite a series of provocative and highly interesting published studies GPR120 remains poorly validated as a therapeutic target. As such, the most direct beneficiaries of this research within the private commercial sector will be those working in the pharmaceutical industry. Our research will assist this sector in a number of ways. Firstly, for poorly validated GPCRs that have not previously been the targets of sustained effort within the pharmaceutical industry there are often a paucity of suitably selective pharmacological tools to define receptor function. This is true of GPR120 and the ligands we have already described and will continue to develop can be synthesised within the commercial sector and used as reference ligands to support their own work. Secondly, our research will provide important guidance and answers to key questions that remain uncertain from the currently published work. These outcomes may encourage or (just as importantly) dissuade companies from investing heavily in programmes to target this receptor. Thirdly, although the concept of ligand and receptor bias in function is well established conceptually within the academic research community and when using in vitro cell-based assays, this has yet to be adopted whole heartedly by the commercial sector. In part this reflects that although GPCRs can signal via a variety of mechanisms the significance of this for physiology is unknown and, therefore, it is unclear to the commercial sector if biased ligands offer unique commercial opportunities in different therapeutic areas. Our studies employing the phosphorylation-deficient form of GPR120 are likely to help define this.
Finally, although the applicants have strong and long term links with the pharmaceutical sector, the proposed collaboration will allow us to perform studies with a breadth of scope and concept that neither could achieve separately. This will result in even stronger links to the pharmaceutical industry that will impact to the benefit of both sides as we move to address questions linked directly to the major intellectual and practical challenges facing the industry to translate basic science into commercial products.
Translation of basic research to the production of approved medicines is a long and challenging process, typically taking between 10-12 years. However, greater confidence in the selected target, based on the type of studies proposed herein, may improve company performance. In the longer term, if successful this would potentially improve quality of life for many individuals as chronic diseases associated with aging and poor nutritional selection are increasing burdens on economies. Inflammation is implicated in the development of many such diseases including metabolic disorders and vascular/heart disease. Targetting GPR120 may offer a novel approach. The studies will also impact on training of staff who may move subsequently into the commercial health research sector. The breadth of approaches and skills that the post-doctoral fellows will be exposed to will range from medicinal chemistry design to transgenic amimal studies and equip them with excellent skills sets for their future careers.
Who will benefit from this research and how will they benefit?
This receptor is attracting considerable interest as a potential novel therapeutic target at the interface between inflammation and chronic metabolic disease. However, despite a series of provocative and highly interesting published studies GPR120 remains poorly validated as a therapeutic target. As such, the most direct beneficiaries of this research within the private commercial sector will be those working in the pharmaceutical industry. Our research will assist this sector in a number of ways. Firstly, for poorly validated GPCRs that have not previously been the targets of sustained effort within the pharmaceutical industry there are often a paucity of suitably selective pharmacological tools to define receptor function. This is true of GPR120 and the ligands we have already described and will continue to develop can be synthesised within the commercial sector and used as reference ligands to support their own work. Secondly, our research will provide important guidance and answers to key questions that remain uncertain from the currently published work. These outcomes may encourage or (just as importantly) dissuade companies from investing heavily in programmes to target this receptor. Thirdly, although the concept of ligand and receptor bias in function is well established conceptually within the academic research community and when using in vitro cell-based assays, this has yet to be adopted whole heartedly by the commercial sector. In part this reflects that although GPCRs can signal via a variety of mechanisms the significance of this for physiology is unknown and, therefore, it is unclear to the commercial sector if biased ligands offer unique commercial opportunities in different therapeutic areas. Our studies employing the phosphorylation-deficient form of GPR120 are likely to help define this.
Finally, although the applicants have strong and long term links with the pharmaceutical sector, the proposed collaboration will allow us to perform studies with a breadth of scope and concept that neither could achieve separately. This will result in even stronger links to the pharmaceutical industry that will impact to the benefit of both sides as we move to address questions linked directly to the major intellectual and practical challenges facing the industry to translate basic science into commercial products.
Translation of basic research to the production of approved medicines is a long and challenging process, typically taking between 10-12 years. However, greater confidence in the selected target, based on the type of studies proposed herein, may improve company performance. In the longer term, if successful this would potentially improve quality of life for many individuals as chronic diseases associated with aging and poor nutritional selection are increasing burdens on economies. Inflammation is implicated in the development of many such diseases including metabolic disorders and vascular/heart disease. Targetting GPR120 may offer a novel approach. The studies will also impact on training of staff who may move subsequently into the commercial health research sector. The breadth of approaches and skills that the post-doctoral fellows will be exposed to will range from medicinal chemistry design to transgenic amimal studies and equip them with excellent skills sets for their future careers.
People |
ORCID iD |
Andrew Tobin (Principal Investigator) |
Publications
Alvarez-Curto E
(2016)
Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling
in Journal of Biological Chemistry
Bolognini D
(2016)
A Novel Allosteric Activator of Free Fatty Acid 2 Receptor Displays Unique Gi-functional Bias.
in The Journal of biological chemistry
Bradley SJ
(2018)
The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system.
in Neuropharmacology
Bradley SJ
(2018)
Muscarinic acetylcholine receptors in the central nervous system.
in Neuropharmacology
Brightling CE
(2019)
Fatty airways: a source of good and bad fats?
in The European respiratory journal
Milligan G
(2017)
FFA4/GPR120: Pharmacology and Therapeutic Opportunities.
in Trends in pharmacological sciences
Prihandoko R
(2020)
Pathophysiological regulation of lung function by the free fatty acid receptor FFA4.
in Science translational medicine
Prihandoko R
(2016)
Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free Fatty Acid Receptor 4/G Protein-Coupled Receptor 120.
in Molecular pharmacology
Tobin A
(2020)
Editorial for Advances in G Protein-Coupled Receptor Signal Transduction Special Issue
in ACS Pharmacology & Translational Science
Description | we have found that GPR120 regulates airway smooth muscle relaxation |
Exploitation Route | This receptor may be a novel target in human inflammatory airway disease |
Sectors | Pharmaceuticals and Medical Biotechnology |
Description | Clinical collaboration on inflammatory lung disease |
Organisation | University of Leicester |
Department | Leicester Medical School |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Support for the targeting of FFA4 in inflammatory lung disease |
Collaborator Contribution | Clinical samples and drug trials |
Impact | Outcome has been to establish FFA4 as a validated target in inflammatory lung disease |
Start Year | 2018 |
Description | Cell block Science - Low moss Bishop Briggs, Glasgow. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Workshop for prisoners |
Year(s) Of Engagement Activity | 2018 |
Description | Cell block Science - Shotts Prison, Glasgow. |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Talk to prisoners |
Year(s) Of Engagement Activity | 2018 |
Description | Cold Spring Harbor, Asia, Membrane Proteins: From Physiology to Pharmacology. Suzhou, China. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation of research data |
Year(s) Of Engagement Activity | 2019 |
Description | Keystone presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Keystone science conference |
Year(s) Of Engagement Activity | 2017 |
Description | Presentation to subcommittee on Life Sciences, Scottish Parliament on the impact of Brexit |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Presented to the subcommittee on Life Sciences |
Year(s) Of Engagement Activity | 2019 |
Description | Protein kinase inhibitor (PKI) meeting. Warsaw, Poland. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation of research data |
Year(s) Of Engagement Activity | 2019 |
Description | |Glasgow science fair 2017 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Stand at the science fair in central Glasgow |
Year(s) Of Engagement Activity | 2017 |
Description | • Pint of Science - Raven pub, Glasgow. June 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | 50 members of the general public at this outreach event |
Year(s) Of Engagement Activity | 2018 |