Marc Joiret 's web space Thesis and publications e-mail icon

I did my third master thesis as a host student at the GIGA-R (BIO3 research team) in Liege.
Title : « The impact of correlated genetic markers on large-scale DNA based gene-gene interaction studies ».
Here is my Biostatistics / Bioinformatics Master thesis in PDF format.
Supervisers:

My PhD research topic addresses the computational modeling of protein synthesis by ribosomes.
Title : « mRNA translation rate modeling with extended TASEP incorporating tRNAs modifications effects ».

Abstract:
Translational regulation through synonymous codon usage has been recently shown to play an important role in health and disease. Modified tRNAs are important actors involved in regulating protein expression levels by optimizing the decoding of differentially used codons, nevertheless their contribution in protein synthesis dynamics remain unclear. Totally Asymmetric Simple Exclusion Process (TASEP) models have been used to quantify the transcripts translation rate by ribosomes. Our work aims at extending TASEP modeling to accommodate for tRNA modifications effects. We will generate a computational stochastic model quantifying protein synthesis rates. The algorithm uses ribosome residence time per codon from transcripts codons sequences, relative transcripts abundance and tables of (modified or not) tRNA relative abundance. Important features in the model include the elongation rate variation caused by charged amino-acids in the ribosomal exit tunnel, proline ring opening delay at the peptide transfer center and transcript secondary structure slow down effects. The model allows to compare relative protein expression levels as well as RiboSeq profiles in different scenarios with a controllable pool of ribosomes. We intend to use our model to help understand how codon usage and tRNA modifications dynamically interact and impact on protein synthesis. The ultimate purpose of the work is to understand how the translational control through codon usage and tRNA tuning influence local protein structure possibly leading to changes in functional specific activity, aggregation, autophagy or proteasomal degradation. The results of this work will possibly help the development of targeted therapies against melanomas.

Supervisers:

Biostatistics, Bioinformatics and Computational Biology

Joiret, M., Mahachie John, J.M., Gusareva, E.S, Van Steen, K. Confounding of linkage disequilibrium patterns in large scale DNA based gene-gene interaction studies. BioData Mining, 2019.
For open access to the paper, click here.

Joiret, M., Rapino, F., Close, P., Geris, L. mRNA translation rate modeling with an extended TASEP incorporating tRNAs modifications. Poster at EMBO Workshop, Heidelberg, Sep 04-07, 2019.
For open access to the poster, click here.

Zappia, J.,Joiret, M., Sanchez, C., Lambert, C., Geris, L., Muller, M., Henrotin, Y. From translation to protein degradation as mechanisms for regulating biological functions: A review on the SLRP family in skeletal tissues. Biomolecules, 2020.
For open access to the paper, click here.