Mots-Clés

prion-like proteins, molecular evolution

Description

Exploring the Molecular Evolution and origin of Prion-Like Proteins Across the Tree of Life

Prion-like proteins, also known as prion-related proteins, are a class of proteins that share structural and functional similarities with infectious prions but do not exhibit the same pathological behavior. While the specific functions of prion-like proteins can vary widely depending on the protein in question and the organism it is found in, they are generally associated with several important cellular processes. However, the evolution and distribution of prion-like proteins across diverse organisms remain poorly understood and the recent discovery of prions in bacteria, archaea and viruses has intimated a potentially more ancient evolutionary origin. We propose a 6 months internship in bioinformatics and computational biology to identify and investigate the molecular evolution of prion-like proteins across the tree of life, elucidating their origin, functional diversity, and potential implications in different organisms. The internship will take place the young and new computational biology team of the SEPIA located in Fontenay-aux-Roses, France nearby Paris under the supervision of Amin Madoui (CEA researcher). This internship is a first step for a PhD thesis on the same topic.

Objectives:

1. Identification of prion-like proteins in the tree of life
2. Construct a comprehensive phylogenetic tree incorporating representative species from various taxa to elucidate the evolutionary relationships of prion-like proteins across the tree of life.
3. Investigate the role of gene duplication events in the expansion of prion-like protein families, analyzing patterns of sequence divergence and conservation.
4. Perform functional annotation of identified prion-like proteins, predicting potential functional domains, interactions, and involvement in cellular pathways.
5. Explore the signals of positive selection acting on prion-like proteins in different lineages, investigating the relationship between adaptive changes and ecological or physiological factors.
6. Reconstruct the evolution of a subset of prion-like proteins involved in key cellular processes.

Methodology:

Data Collection: Retrieve protein sequences from a wide range of organisms, representing various taxonomic groups, using public databases and omics data using state-of-the arts methods.

Phylogenetic tree:  phylogenetic methods to construct a robust phylogenetic tree.

Gene Evolution Analysis: Utilize computational tools to detect gene duplication events, infer rates of sequence evolution, and identify conserved motifs.

Functional Annotation: Employ bioinformatics tools to predict functional domains, protein interactions, and pathway associations.

Positive Selection Analysis: Apply evolutionary genetics models to detect sites under positive selection, using statistical methods to correlate selection signals with environmental variables.

Candidate profile:

Master student in bioinformatics or similar background

Good knowledge of Linux and Bash

Good programming skills in perl or python

Statistic with R

Salary:

The students will receive around 700€ per months

References:

Tomasz Zajkowski, Michael D Lee, Shamba S Mondal, Amanda Carbajal, Robert Dec, Patrick D Brennock, Radoslaw W Piast, Jessica E Snyder, Nicholas B Bense, Wojciech Dzwolak, Daniel F Jarosz, Lynn J Rothschild, The Hunt for Ancient Prions: Archaeal Prion-Like Domains Form Amyloid-Based Epigenetic Elements, Molecular Biology and Evolution, Volume 38, Issue 5, May 2021, Pages 2088–2103, https://doi.org/10.1093/molbev/msab010

Sabate R, Rousseau F, Schymkowitz J, Ventura S (2015) What Makes a Protein Sequence a Prion?. PLOS Computational Biology 11(1): e1004013. https://doi.org/10.1371/journal.pcbi.1004013