PIK signalling in Immunity and Infection
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
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.
Technical Summary
The developed world has observed a dramatic reduction in mortality due to infections over the last century. At the same time, certain cancers, allergy and autoimmune disease are on the rise. Moreover, re-emerging and novel pathogens such as HIV, flu and various bacterial infections target vulnerable populations everywhere. As a consequence, a substantial effort is still required to find strategies to target the immune system in ways that reduce autoimmune, allergic and inflammatory diseases while retaining optimal protection from pathogens. In this programme, we will explore how experimental and eventually therapeutic modulation of the PI3K signalling module affects different components of the immune system. We will apply this knowledge to suggest how manipulation of PI3K signalling can be used to promote immunological health and improved lifespan.
Planned Impact
unavailable
Organisations
Publications
Angulo I
(2013)
Phosphoinositide 3-kinase d gene mutation predisposes to respiratory infection and airway damage.
in Science (New York, N.Y.)
Benson RA
(2018)
Non-Invasive Multiphoton Imaging of Islets Transplanted Into the Pinna of the NOD Mouse Ear Reveals the Immediate Effect of Anti-CD3 Treatment in Autoimmune Diabetes.
in Frontiers in immunology
Bouabe H
(2013)
A protocol for construction of gene targeting vectors and generation of homologous recombinant embryonic stem cells.
in Methods in molecular biology (Clifton, N.J.)
Bouabe H
(2013)
Gene targeting in mice: a review.
in Methods in molecular biology (Clifton, N.J.)
Garçon F
(2016)
PI3Kd promotes CD4 + T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1
in Immunology & Cell Biology
Lau D
(2020)
Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model.
in Frontiers in immunology
Lim EL
(2019)
Phosphoinositide 3-kinase d is a regulatory T-cell target in cancer immunotherapy.
in Immunology
Lucas C
(2016)
PI3Kd and primary immunodeficiencies
in Nature Reviews Immunology
Okkenhaug K
(2016)
Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy
in Cancer Discovery
Okkenhaug K
(2013)
Signaling by the phosphoinositide 3-kinase family in immune cells.
in Annual review of immunology
| Description | We have generated new a new mouse model mimicking a newly described primary immune deficiency which will help us understand why APDS patients are susceptible to airway infections. |
| First Year Of Impact | 2014 |
| Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Gilead Oncology Faculty |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Following the EMA approval of Zydelig® (idelalisib) in September 2014, and the presentation of new data on idelalisib at ASH 2014, Gilead medical affairs launched a new idelalisib speaker programme, known as "Gilead Oncology Faculty". This medically led, non-promotional activity aims to provide engaged experts the opportunity to be trained on idelalisib data of high quality and scientific content (on label; new indications and new oncology drugs within the Gilead portfolio to be added according to their approval) and subsequently, to give Gilead affiliates across the EMEA region engagement opportunities with registered haematology experts for their local / regional non-promotional speaking events. |
| URL | https://www.gileadfaculty.com |
| Description | Enhancing T cell immunity to cancer metastasis |
| Amount | £3,116,755 (GBP) |
| Funding ID | MR/Y013301/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 03/2029 |
| Description | ITN PIPgen |
| Amount | € 4,099,075 (EUR) |
| Funding ID | 955534 |
| Organisation | Marie Sklodowska-Curie Actions |
| Sector | Charity/Non Profit |
| Country | Global |
| Start | 06/2021 |
| End | 06/2025 |
| Description | MRC MICA programme grant |
| Amount | £1,000,000 (GBP) |
| Funding ID | MR/M012328/2 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2015 |
| End | 01/2019 |
| Title | Cinical trial of GSK |
| Description | Based on the discovery of Activated PI3K Delta Syndrome (APDS) GSK has announced a clinical trial of their Pi3Kd inhibitor GSK2269557. This is supported by and MRC-MICA award, but build on work we have done on PI3Kd, including discovery that APDS leads to hyperactive PI3Kd in T cells. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2015 |
| Development Status | Under active development/distribution |
| Impact | Another trial has been announced by Novartis. |
| URL | https://clinicaltrials.gov/ct2/show/NCT02593539 |
| Description | Discussed animal research on Cambridge TV |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | I was interviewed for a programme aired on Cambridge TV about the use of animals in research. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.cambridge-tv.co.uk/impact-animal-research/ |
| Description | Royal Society Summer Exhibition, 2015: Immune Army |
| 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 | We presented our exhibition: "Immune Army: weapons of microscopic destruction"; at the Royal Society Summer exhibition 2015. Many members of my lab participated in the design of the exhibition materials, the accompanying video (https://youtu.be/oMj8UxMPYJU) and at the exhibition itself. I spent two full days at the exhibition. Work on Activated PI3K Delta Syndrome (APDS) and Cancer immunotherapy from my lab featured prominently in this exhibition. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://sse.royalsociety.org/2015/immune-army/ |