Prof. Dr. Elena Rugarli

Research Area: Mitochondrial Dysfunction and Neurodegeneration

Website: Rugarli Lab

1. Research Background:

Mitochondria are essential organelles involved in ATP production, Fe-S cluster biogenesis, calcium buffering, and several metabolic biosynthetic pathways. Mitochondrial homeostasis depends on regulated biogenesis and efficient quality control mechanisms, and is key to cell survival. Dysfunctional mitochondria can trigger apoptotic cell death, and play an important role in the pathogenesis of several ageing-associated diseases, including hereditary spastic paraplegia, a disease characterized by the degeneration of central motor axons. We are especially interested in understanding how is the quality of mitochondria maintained in long axons during our life-time.

2. Research questions addressed by the group:

We are interested in answering the following questions:

  • Which cellular pathways are involved in maintaining the viability of long motor axons?
  • How is the quality and function of mitochondria regulated, especially in neurons and along axons?

To address these questions, we study the basic function of genes involved in hereditary spastic paraplegia, a genetic disease characterized by degeneration of the central motor axons. In addition, we unravel basic biological mechanisms that maintain the quality of mitochondria, including intra-organellar proteases and post-transcriptional regulators of mRNAs encoding mitochondrial proteins.

3. Possible projects:

  • Identification of novel post-transcriptional regulators of mitochondrial gene expression in neurons;
  • Strategies to boost mitochondrial function and prevent ageing-associated neuronal degeneration.

4. Applied Methods and model organisms:

  • Model organisms: transgenic mice.
  • Methods: Genetics, advanced microscopy, mass spectrometry, molecular biology, systems biology (transcriptomics, proteomics, metabolomics), biochemistry, histochemistry.

5. Desirable skills and qualifications:

We are looking for candidates with a solid background knowledge acquired during master studies (biology, neuroscience, biochemistry, biotechnology), high motivation to be part of a dynamic team, and passion and enthusiasm for science.

6. References:

  • Tadepalle, N. and Rugarli, E.I. (2021).  Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia. Front. Mol. Biosci., 10 May 2021. 8:673977. doi: 10.3389/fmolb.2021.673977. eCollection 2021. Review
  • Tadepalle, N., Robers, L. Veronese, M. Zentis, P. , Babatz, F. Brodesser, S. Gruszczyk, A.V., Schauss, A., Hoening, S., and Rugarli, E. I. (2020). Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis Life Sci. Alliance 3 (6):e202000715.
  • Pla-Martin, D.,  Schatton, D., Wiederstein, J.L., Marx, M.C.,  Khiati, S., Krüger, M., and Rugarli, E.I. (2020). CLUH granules coordinate translation of mitochondrial proteins with mTORC1 signaling and mitophagy. EMBO J 39(9):e102731.
  • Murru, S., Hess, S., Barth, E., Almajan, E.R., Schatton, D., Hermans, S., Brodesser, S., Langer, T., Kloppenburg, P. and Rugarli, E.I. (2019). Astrocyte‐specific deletion of the mitochondrial m‐AAA protease reveals glial contribution to neurodegeneration. Glia 67(8):1526-1541.
  • Schatton, D. and Rugarli, E.I. (2018). A concert of RNA-binding proteins coordinates mitochondrial function. Crit Rev Biochem Mol Biol 53(6):652-666.
  • Schatton, D., Pla-Martin, D., Marx, M.C., Hansen, H., Mourier, A., Nemazanyy, I., Pessia, A., Zentis, P., Corona, T., Kondylis, V., Barth, E., Schauss, A.C., Velagapudi, V., and Rugarli, E.I. (2017). CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs. J Cell Biol. 216: 675-693.
  • Gao J., Schatton D., Martinelli P., Hansen H., Pla-Martin D., Barth E., Becker C., Altmueller J., Frommolt P., Sardiello M., Rugarli, E.I. (2014) CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins. J Cell Biol, 207(2):213-23. doi: 10.1083/jcb.201403129.