Periodic Reporting for period 2 - IMAP (Integrative mechanistic and multi-omics Modelling of Antigen Presentation to predict epitope dynamics)
Reporting period: 2022-10-01 to 2024-03-31
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.
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.
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.
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.
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.