Dr. Mafalda Escobar-Henriques

Research Area: 1-Cell autonomous Control of homeostatic Mechanisms and cellular Stress Responses in Ageing and age-associated Diseases

Website: https://www.cecad.uni-koeln.de/research/principal-investigators/dr-ana-mafalda-escobar-henriques-dias/

1. Research Background:

Our team is interested in mitochondrial dynamics and quality control, which are critical during aging. Mitochondria are constantly remodeled by fusion and fission events, which are mediated by the dynamin-related proteins (DRP) mitofusins and DRP1, respectively. We found that ubiquitin is necessary to keep mitochondria and cells in a plastic and healthy state. Recently, we identified a novel and unsuspected form of ubiquitin, with a broad and unprecedented impact in all stress responses discovered so far. Now, we focus on how this regulates known but largely unexplored connectionsbetween mitochondria and theautophagic and endocytic pathways.

2. Research questions addresses by the group:

Our research intertwines mitochondria and ubiquitin: We are interested in several aspects of mitochondrial dynamics and quality-control processes, critical for aging processes, which are regulated by ubiquitin:

  1. Identify the disease relevant functions of mammalian mitofusins.
  2. Dissect why and how membrane anchored DRPs promote fusion, rather than fission events. 
  3. Understand new fusion-independent roles of mitofusin ubiquitylation. 
  4. Uncover the interplay between the endocytic machinery and mitochondria.
  5. Investigate the mechanistic features behind stress management by ubiquitin.

3. Possible projects:

Several projects addressing the questions outlined before are possible and should be directly discussed, to find the best interest match between the PhD candidate and our group.

4. Applied Methods and model organisms:

We use biochemistry, molecular biology, genetics and cellular biology, mainly in the model organism S. cerevisiae. To be able to transfer the relevance of our findings to disease states, we now developed new model systems of mitofusins, using human cell lines. We have several ongoing collaborations with research groups complementing our expertise. Moreover, aiming at a concrete possibility to provide therapies of disease-associated functions of mitofusins, we started joining forces with the clinicians.

5. Desirable skills and qualifications:

Most important are scientific curiosity, motivation, flexibility, resilience and team work skills. Previous experience with yeast or cell culture is beneficial but not required.

6. References:

  1. M. Escobar-Henriques, S. Altin and F. den Brave (2019) “Interplay between the Ubiquitin Proteasome System and Mitochondria for Protein Homeostasis.” Curr. Issues Mol. Biol. Aug 18;35:35-58. Review.
  2. M. Escobar-Henriques and M. Joaquim (2019) "Mitofusins: Disease Gatekeepers and Hubs in Mitochondrial Quality Control by E3 Ligases.”, Front Physiol. May 9;10:517. Review.
  3. T. Simões, R. Schuster, F. den Brave and M. Escobar-Henriques (2018) “Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion”,Elife. Jan 8 e30015.