Postdoctoral position at the ULB Center for Diabetes Research

Applications are invited for 1 postdoctoral position in Mariana Igoillo-Esteve research group at the ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.

The ULB Center for Diabetes Research is an international laboratory, hosting around 28 members across 4 research teams focused on different aspects of type 1, type 2 and monogenic diabetes.

Website of the center: https://www.ulbcdiabres.com/

The Igoillo-Esteve team studies the molecular mechanisms of β-cell dysfunction and death in type 2 diabetes and monogenic forms of diabetes, with the ultimate goal to identify novel strategies to prevent β-cell demise. The elucidation of disease mechanisms in monogenic forms of diabetes contributes to further the understanding of β-cell failure not only in these rare diseases, but also in polygenic type 1 and type 2 diabetes, and to propose tailored therapeutic strategies.

In particular, the Igoillo-Esteve research group studies the loss of functional β-cell mass related to endoplasmic reticulum stress and altered tRNA modifications, two biological pathways contributing to β-cell failure in monogenic and type 2 diabetes.

Dr. Igoillo-Esteve’s recent findings indicate that tRNA methylation is essential for β-cell survival, and that hypomodified tRNAs are prone to enzymatic cleavage leading to tRNA fragment generation (1-4). tRNA halves and smaller tRNA fragments are a new class of small non-coding RNAs that modulate several cellular processes by inhibiting translation or transcription of specific mRNAs. Through high quality, innovative, and disease-relevant research Dr Igoillo-Esteve is expanding knowledge on tRNA biology in pancreatic β-cells and shedding light on this new pathway of β-cell failure relevant to monogenic and polygenic forms of diabetes.

The open position is intended to elucidate the implications of reduced expression of TRMT10A (a tRNA methyltransferase), impaired tRNA methylation, and tRNA fragmentation on the development of type 1 diabetes. The project involves targeted and high throughput experiments using different in vitro models of TRMT10A deficiency including RNAi-mediated gene silencing in human β-cells, iPSC-derived β-cells from TRMT10A-deficient patients and control individuals, and CRISPR/Cas-9-mediated TRMT10A knockout iPSC-derived β-cells.

The candidate must hold a PhD degree in biology, molecular biology, or similar; have a strong interest in human disease and be able to work autonomously.

Experience in cell, molecular and/or RNA biology (e.g. miRNAs, tRNA, non-coding RNAs) is considered a must. Experience in stem cell biology is not required but it will be considered as a plus.

The fellowship is available from 01/03/2022 and has an initial duration of one year. The contract will be renewed for further two years if the candidate shows adequacy for the position.

Applications are accepted until the position is filled. Please e-mail a letter of interest, curriculum vitae (including publication list), and the name of 2-3 reference persons (with email address and telephone number) to:

Prof Mariana Igoillo-Esteve, PhD

Mariana.igoillo.esteve@ulb.be

ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium

Publications by the PI related with the project

1. Igoillo-Esteve, M., Genin, A., Lambert, N., Desir, J., Pirson, I., Abdulkarim, B., Simonis, N., Drielsma, A., Marselli, L., Marchetti, P. et al. (2013) tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans. PLoS Genet, 9, e1003888.

2. Cosentino, C., Toivonen, S., Diaz Villamil, E., Atta, M., Ravanat, J.L., Demine, S., Schiavo, A.A., Pachera, N., Deglasse, J.P., Jonas, J.C. et al. (2018) Pancreatic beta-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes. Nucleic Acids Res, 46, 10302-10318.

3. Cosentino, C., Cnop, M. and Igoillo-Esteve, M. (2019) The tRNA epitranscriptome and diabetes: emergence of tRNA hypomodifications as a cause of pancreatic beta-cell failure. Endocrinology.

4. Arroyo, M.N., Green, J.A., Cnop, M. and Igoillo-Esteve, M. (2021) tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors. Int J Mol Sci, 22.