The research group led by Assistant Prof. Xavier Bofill-De Ros at the Department of Molecular Biology and Genetics, Aarhus University, is looking for motivated postdoctoral candidates to jointly apply for a personal fellowships (typically MSCA plus others). The group is broadly interested in studying how dysregulation of microRNA homeostasis contributes to pathogenesis.
Candidates with strong expertise in disease models (eg. neurological, endocrinology, hematology, dermatology) are strongly encouraged to build on their current expertise while developing new skills on microRNA function. Discussion of joint interests will be elaborated during the formulation of the specific project proposal. In addition, the Department of Molecular Biology and Genetics (https://mbg.au.dk/) provides access to a wide range of resources (eg. biophysics, mice, zebrafish cores) and complementary expertise.
The research project will be funded with the current Lundbeck Foundation starting grant (~1,34M€). Opportunities for additional project funding will be encouraged to support the development of the candidate’s career.
MicroRNAs (miRNAs) are a class of small non-coding RNAs with essential roles in gene expression. Together, miRNAs regulate the expression of >60% of genes and deficiencies in their maturation, as well as their levels within cells have been shown to drive several diseases including cancer. miRNAs are transcribed as longer transcripts (pri-miRNAs), the maturation of which requires the adequate RNA folding and the precise endonucleolytic cleavage of DROSHA and DICER1. This processing is aided by more than 180 RNA-binding proteins. The resulting products are mature miRNAs that provide specificity to Argonaute (AGO), a key component in RNA silencing. Thus, the malfunction of components of the biogenesis pathway can result in various molecular phenotypes such as aberrant products, localization, or stability.
It has been proposed that dysregulation of RNA-binding proteins can promote defects in miRNA biogenesis. For example, affected miRNA precursors may yield aberrant expression levels, strand selection or altered specificities for mRNA targets. Understanding the role of co-factors in miRNA biogenesis will pave the way to the development of therapeutic targets aimed at regulating miRNA function.
Decay of miRNAs is of particular interest since half-lives of miRNAs range between hours and days. For example, cardiac-specific miR-208 has a half-life of ~2 weeks, while others, such as miR-16 can decay within minutes in response to cell cycle phases or changes in light-darkness in retinal neurons. Despite these disparities in their stability, little is known about the molecular mechanisms that regulate miRNA decay under physiological and pathological conditions.
** Marie Curie Postdoctoral Fellowship (MSCA PF) Masterclass 2024 from AU Research Support Office.
Contact us "bofillderoslab+candidates" "at" "gmail" "dot" "com" with the headline "POSTDOC 2024 - CANDIDATE NAME".
Include in your application:
Cover letter
CV
References
Yang A*, Bofill-De Ros X*, Stanton RC, Shi C, et al. “TENT2, TUT4 and TUT7 selectively regulate miRNA sequence and abundance”. Nature Communications (2022)
Bofill-De Ros X#, Hong Z, Birkenfeld B, et al. “Flexible pri-miRNA structures enable tunable production of 5’ isomiR”. RNA Biology (2022)
Yang A*, Shao TJ*, Bofill-De Ros X*, Lian C, Villanueva P, Dai L, Gu S. “AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2”. Nature Communications (2020)
Yang A*, Bofill-De Ros X*, et al. “3’ uridylation Confers miRNAs with novel non-canonical target repertoires”. Molecular Cell (2019)
Bofill-De Ros X, et al. “Structural differences between pri-miRNA paralogs promotes alternative Drosha cleavage and expands target repertoires”. Cell Reports (2019)