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January 13th 2023

Week 0 : New beginnings

Hello, welcome to the weeknotes for the "histo" project. First an introduction and some background.

I'm Chris, I'm a bioinformatician/software developer/immunologist. I have been awarded an EMBL and the Marie Skłodowska-Curie Actions (MSCA) ARISE fellowship to build tools for immunologists to use. Primarily the tools are related to the Class I and Class II molecules of the Major Histocompatibility Complex that present antigen to T-cells.

The aim of the work is to pull together data and tools to allow immunologists, structural biologists and machine learning developers to answer some specific questions such as these below:

  • what governs the motif and conformation of peptides bound to MHC molecules and how does this change the shape of the peptide binding cleft
  • what governs the three-dimensional recognition of MHC:peptide complexes by T-cells
  • what data exists about peptide repertoires and how can this data be used to extrapolate to MHC alleles with no data
  • what is the structural variability between MHC alleles, MHC molecules of different species and between specific MHC:peptide complexes and how can this information be used predictively
  • what is the role of each position within the MHC molecule, and how can this data be used to explain biological phenomena (such as TAPBPR dependence and independence)
  • what can we understand from data about the effects of peptide processing and transcript level in the cell to better predict epitope sequences

The aim of the ARISE fellowship is to learn how to build and deliver "research infrastructures" such as "histo". These will be built using user-centric design/development methods and, in this case in particular, by "working in the open". This means that I'll be sharing the process as well as the outputs/outcomes so that as much of the learning can be shared as quickly as possible. Hopefully, there will be publications involved in this process, but these "weeknotes" will help as a regular and immediate view into the project.