In Silico Modelling of Toll-Like Receptor Pathways in Human Epidermal Keratinocytes
Lead Research Organisation:
University of Southampton
Department Name: Clinical and Experimental Sciences
Abstract
The discovery, that the epithelial surfaces, such as skin, can actively programme systemic immune responses has revolutionized our understanding of human immunity. To fully harness this exciting finding, it is essential to dissect the molecular interactions orchestrating the process of immune programming. Our recent research identified the key molecular networks regulating antigen presentation by human skin immune cells, and documented the power of stochastic modelling for prediction of different functional immunity outcomes (Polak et al, 2017, Nature: Scientific Reports 7:668; Livigni et al Nature Protocols, 2018, in press).
The aim of this PhD project is to identify, reconstruct, and model in vitro and in silico, gene regulatory networks of host-pathogen interactions in human skin, developing a novel platform for in silico investigation of immunity.
Specific objectives:
1. Identification of molecular networks in human skin.
2. Assembling of an in silico representation of the key gene regulatory network.
3. Dynamic modelling of the in silico model to investigate immune responses in human intact epidermis.
4. Targeting human keratinocytes to modulate function.
The aim of this PhD project is to identify, reconstruct, and model in vitro and in silico, gene regulatory networks of host-pathogen interactions in human skin, developing a novel platform for in silico investigation of immunity.
Specific objectives:
1. Identification of molecular networks in human skin.
2. Assembling of an in silico representation of the key gene regulatory network.
3. Dynamic modelling of the in silico model to investigate immune responses in human intact epidermis.
4. Targeting human keratinocytes to modulate function.
Organisations
People |
ORCID iD |
| Marta Ewa Polak (Primary Supervisor) | |
| Gemma Porter (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/R505456/1 | 30/09/2018 | 02/09/2022 | |||
| 2137542 | Studentship | BB/R505456/1 | 30/09/2018 | 02/09/2022 | Gemma Porter |
| Title | Genetic Algorithm |
| Description | I have developed a genetic algorithm which is able to estimate parameter values for mathematical models. These parameter values can be utilised to enhance the predictive capabilities of in silico models. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | This algorithm is still in development, but it appears to be an improvement on current techniques for parameter estimation and we are in the process of submitting a publication. |
| Description | Defend the Skin Competition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | We ran a Hampshire - wide competition for secondary school pupils. The competition required students to develop their own computer or board game that teaches the player about skin immunology. Participants had to produce a video to explain their game and finally present their games at the grand final in front of the judging panel. We will also be organising a showcase session for the games at a local board game cafe. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://sig-labs.com/defend-the-skin-games/ |
| Description | New Forest & Hampshire County Show |
| 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 | I attended the New Forest and Hampshire County Show in July 2019. We ran a stall with an activity aimed at educating the public on the importance of skin immunology. Around 100 children plus their parents/carers took part in the activity, where they had to make a model of the skin using salt dough. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Southampton Science and Engineering Festival |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | I designed a set of activities relating to the skin immune system for the Southampton Science and Engineering Festival 2020. These activities were made available via the University of Southampton SOTSEF website for the general public to download. |
| Year(s) Of Engagement Activity | 2020 |