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:
- Prof. Dr. Dr. Kristel Van Steen (KUL, ULiege);
- Prof. Dr. Ziv Shkedy (UHasselt).
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.
Supervisor & co-supervisor:
- Prof. Dr. ir. Liesbet Geris (ULiege - Biomech - GIGA in silico medicine);
- Prof. Dr. Pierre Close (ULiege - Cancer signaling - GIGA Stem Cells).
Biostatistics, Bioinformatics, Biophysics, Biochemistry and Computational Biology
Joiret, M., Kerff, F., Rapino, F., Close, G., Geris, L. A simple model of the electrostatics environment around the catalytic center of the ribosome and its significance for the elongation cycle kinetics. Computational and Structural Biotechnology Journal 21, pp.3768-3795, 2023.
For access to the paper, click here.
Joiret, M., Leclercq, M., Lambrechts, G., Rapino, F., Close, P., Louppe, G., Geris, L. Cracking the genetic code with neural networks. Frontiers in Artificial Intelligence 6, 59, 1128153, 2023.
For access to the paper, click here.
Joiret, M., Rapino, F., Close, P., Geris, L. A simple model of the electrostatics environment around the catalytic center of the ribosome and its significance for the elongation kinetics. Poster at CSHL meeting, Cold Spring Harbor, Sep 06-10, 2022.
For open access to the poster, click here.
Joiret, M., Kerff, F., Rapino, F., Close, P., Geris, L. Ribosome exit tunnel electrostatics. Physical Review E 105(1), 014409, 2022.
For access to the paper, click here.
Joiret, M., Rapino, F., Close, P., Geris, L. Ribosome exit tunnel electrostatics. Poster at EMBO Workshop, Heidelberg, Sep 07-10, 2021.
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.
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.
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.
GitHub public repository