Sex-bias in the regulation and function of R-loops
1 PhD project offered in the IPP summer call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
Neurological autoimmune disorders occur when the body's defense system mistakenly attacks healthy brain tissue. This group includes conditions like Multiple Sclerosis (MS) and some types of Systemic Lupus Erythematosus (SLE) that affect the nervous system. At the molecular level, these disorders involve complex interactions between the immune system and the central nervous system. A key factor is the overactivation of type 1 interferon, a part of the immune system that recruits immune cells to the central nervous system. This persistent process results in chronic inflammation and tissue damage. At the molecular level, the aberrant formation of RNA-DNA hybrids known as R-loops has been implicated in activating innate responses1. These DNA RNA hybrid structures can form during transcription in brain cells and may contribute to genomic instability and altered gene expression2. A striking feature shared by most autoimmune diseases is a strong female predominance, meaning women are much more likely to develop these disorders than men3. The reasons for this disparity are not fully understood and remain an active area of research.
Interestingly, dietary interventions have shown promise in managing these conditions. The ketogenic diet induces a metabolic shift in the body. Originally developed as a therapeutic approach for epilepsy, this diet has recently proven beneficial in the management of Multiple Sclerosis4. The mechanisms underlying these effects are still being elucidated but may involve sex specific modulation of neuroinflammation and neuroprotection.
PhD Project: Implications of selective escape from X-inactivation in neurodevelopmental disorders
We are seeking an enthusiastic researcher to join our young team exploring sex bias and environmental triggers in neuronal vulnerability. You will investigate the interplay between R-loop accumulation, sex-specific brain dynamics, and metabolic factors in female-biased neurological autoimmune disorders.
You will gain hands-on experience with: Primary cell cultures (human/murine), 2D and 3D neuronal co-cultures, CRISPR/Cas9 engineering, Fluorescence-based imaging and analysis, Multiple Omics assays (e.g. RNAseq, CUT&Tag/RUN, DRIP). We offer a supportive environment, state-of-the-art facilities, and opportunities for interdisciplinary collaboration.
Our ideal Candidate is enthusiastic and an open-minded individual who:
Shows curiosity and passion for understanding complex biological processes from molecular to organismal level.
Has strong will to collaborate, work in a team and contribute to positive lab culture
Enjoys discussing both basic and translational aspects of science.
Previous experience with immunology and/or bioinformatics is a plus.
If you are interested in this project, please select Basilicata as your group preference in the IPP application platform.
Publications relevant to this project
Crossley MP, Song C, Bocek MJ et al. (2023) R-loop-derived cytoplasmic RNA–DNA hybrids activate an immune response. Nature 613, 187–194. Link
Niehrs C, & Luke B. (2020) Regulatory R-loops as facilitators of gene expression and genome stability. Nature reviews. Molecular cell biology, 21(3), 167–178. Link
Fritz HJG, Valsecchi CIK*, Basilicata MF* (2024) Sex as a biological variable in aging: insights and perspectives on the molecular and cellular hallmarks. in press
Bahr LS, Bock M, Liebscher D et al. (2020) Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study. Trials 21, 3. Link