The Role of ERK5 Signalling Macrophage Behaviour During Wound Healing
Lead Research Organisation:
University of Manchester
Department Name: School of Health Sciences
Abstract
Project Description: (maximum of 4,000 characters)
Tissue repair and regeneration require dramatic and coordinated changes in cell behaviour in both wound-resident cells at the site of injury and in distant cells that respond to and are recruited to the injured tissue. In the last decade, the influence of inflammatory cells on wound healing has been shown to be highly significant, as they can function to promote or inhibit wound healing. Discovering the underlying mechanisms controlling the behaviour of inflammatory cells is pivotal to controlling these cells for therapeutic benefit.
It is often very instructive to compare normal processes with diseased processes in order to understand how that process is regulated. Diabetic patients and animal models have severely impaired wound healing and often develop chronic wounds. The inflammatory cells found are dysfunctional and inhibit the wound healing. Specifically, macrophages are critical inflammatory mediators in wounds, and adopt behaviours in response to dynamic environmental cues within the wound. Upregulated macrophage infiltration with a persistent inflammatory phenotype correlates with impaired wound healing, yet the influence of macrophages during the different stages of healthy and impaired wound healing is not fully understood.
One particular signalling pathway of interest is extracellular signal related kinase 5 (ERK5). ERK5 is known to regulate a diverse set of cellular processes including proliferation, migration and angiogenesis as well as inflammation. In particular ERK5 controls the polarization and behaviour of macrophages in tumours. Given the pivotal role of ERK5 in macrophage biology in cancer, there is potential for this to translate to other scenarios where macrophages are key players such as wound healing responses.
Specifically, this project will investigate the role that genetic ablation of ERK5 in keratinocytes of murine models has on wound healing and inflammation and evaluate the translatability of this target with a novel pharmacological intervention in both in vitro and in vivo models.
Tissue repair and regeneration require dramatic and coordinated changes in cell behaviour in both wound-resident cells at the site of injury and in distant cells that respond to and are recruited to the injured tissue. In the last decade, the influence of inflammatory cells on wound healing has been shown to be highly significant, as they can function to promote or inhibit wound healing. Discovering the underlying mechanisms controlling the behaviour of inflammatory cells is pivotal to controlling these cells for therapeutic benefit.
It is often very instructive to compare normal processes with diseased processes in order to understand how that process is regulated. Diabetic patients and animal models have severely impaired wound healing and often develop chronic wounds. The inflammatory cells found are dysfunctional and inhibit the wound healing. Specifically, macrophages are critical inflammatory mediators in wounds, and adopt behaviours in response to dynamic environmental cues within the wound. Upregulated macrophage infiltration with a persistent inflammatory phenotype correlates with impaired wound healing, yet the influence of macrophages during the different stages of healthy and impaired wound healing is not fully understood.
One particular signalling pathway of interest is extracellular signal related kinase 5 (ERK5). ERK5 is known to regulate a diverse set of cellular processes including proliferation, migration and angiogenesis as well as inflammation. In particular ERK5 controls the polarization and behaviour of macrophages in tumours. Given the pivotal role of ERK5 in macrophage biology in cancer, there is potential for this to translate to other scenarios where macrophages are key players such as wound healing responses.
Specifically, this project will investigate the role that genetic ablation of ERK5 in keratinocytes of murine models has on wound healing and inflammation and evaluate the translatability of this target with a novel pharmacological intervention in both in vitro and in vivo models.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013751/1 | 01/10/2016 | 30/09/2025 | |||
| 1916346 | Studentship | MR/N013751/1 | 01/10/2017 | 30/09/2021 | Jason Chu |
| Description | Co-founder of Experimental Designs |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Co-founder of an art and science collaboration project to bring together 12 researchers and 12 artists to generate science inspired art in Manchester Museum's Living Worlds Exhibit. This led to the breaking of barriers between two very different communities and has led to further discussions of future works between several pairings. The art was showcased over a three day exhibition as part of Pint of Science - Creative Reactions (attended by over 130 individuals) and has since been further showcased at the University of Manchester as part of "Post-doc Appreciation Week". |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.instagram.com/experimental_designs_mcr/ |
| Description | MRC I'm a Scientist |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | I took part in MRC's I'm a Scientist event and engaged with secondary school children across the UK using an online chatroom platform. This enabled us to directly chat with students and answered questions about science in general or specifically about our PhD research. We chatted with over 1,400 students over the course of a month - reaching far out schools that may not normally be able to interact with university researchers. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://about.imascientist.org.uk/files/2018/08/MRC-Festival-Zone-2018-Report-Im-a-Scientist.pdf |
| Description | School Visit (Cheadle Hulme High School) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | I visited Cheadle Hulme High School to present my convoluted journey to academia and my research in imaging immunology. This lead to discussions about how to get to further education, and sparked interest in modern and historical immunology. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Sub-editor for Research Hive |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I contribute to the Doctoral Academy blog: Research Hive, as the well-being subeditor to highlight opportunities and support available at the University of Manchester. |
| Year(s) Of Engagement Activity | 2018,2019,2020 |
| URL | https://manchesterresearchhive.wordpress.com/ |
| Description | WP Fellow Workshop and Talks |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | I was recently appointed the role of WP Fellow (1 year position) to develop and run several science workshops throughout the year specifically to WP schools and student. This programme enables students from under-served backgrounds to attain better opportunities and awareness of science topics in further education. Typically this involves making workshops and talks for school classes of about 20-30 students. |
| Year(s) Of Engagement Activity | 2018 |