Integrative mechanistic and multi-omics Modelling of Antigen Presentation to predict epitope dynamics

Project Information

IMAP

Grant agreement ID: 945528

DOI

10.3030/945528

EC signature date 13 October 2020

Start date 1 April 2021

End date 31 March 2027

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 495 000,00

EU contribution

€ 1 495 000,00

Coordinated by

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Periodic Reporting for period 3 - IMAP (Integrative mechanistic and multi-omics Modelling of Antigen Presentation to predict epitope dynamics)

Reporting period: 2024-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

The immune response that involves the activity of white blood cells such as CD8 T cells is a pillar of the human defence again cancer and infection. Mankind developed in the last 50 years various molecular biology systems to streamline the immune response such as vaccination and anti-cancer immunotherapies.
In each human being, the CD8 T cells can discriminate between self (good) and non-self (usually bad) by reading ‘antigenic peptides’, which are what cells present at their cell surface through the antigen presentation pathway (APP).
The overall objective of IMAP project aims to understand what are the general rules and dynamics of APP, build a computer model of that, which can then be used in future to streamline vaccinations and immunotherapies. The recent COVID pandemic thought us howe much immunology, vaccination and computer models are a present and future pillar of our society, and the first defence wall in case of epidemies and pandemics.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

From the beginning of the project, IMAP achieved results in all main aims of the project.
We generated laboratory results using specific molecules of the APP, measured their behaviour and used that to build a preliminary version of a computer model (Aim 1; Mechanistic models).
We performed another large set of experiments to measure and describe the cells and how they present the ‘antigenic peptides’ via APP, and generated a preliminary computer model to describe this cellular layer (Aim 2; Multi-omics models).
We started to define how to combine Mechanistic models and Multi-omics models into a single omni comprehensive computer model (Aim 3; Integrated model).
And finally, we applied our acquired knowledge to predict what antigenic peptides’ presented via the APP can be really important in case of infections and cancer, and we tested our predictions in cellular models.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

IMAP project already achieved middle-term results that consolidated some current theories of the immune system function, as well as generated a pool of user-friendly methods and software that could be used by the rest of the scientific community (and of course, in primis, the numerous international collaborators of the project leader Dr. Liepe) to carry out their independent research. Everything achieved so far, upon publishing in journals accessible to any interested reader, is open source in line with principles of research without boundaries.