PhD position: Contributions of ubiquitin signaling to the maintenance of mitochondrial import channels (m/f/d)

Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented, young scientists the chance to work on cutting edge research projects within the open call on “Molecular Mechanisms in Genome Stability & Gene Regulation”. As an IPP PhD student, you will join a community of exceptional scientists working on diverse topics ranging from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory.

Activities and responsibilities

The research group of Axel Methner offers the following PhD project:

TOM complex facilitates protein import into mitochondria, which is vital for their function. Mitochondria-derived vesicles (MDVs) remove faulty TOM proteins, preserving mitochondrial health. The ubiquitin system, involving E3 ligases like MARCH5 and possibly MUL1/MAPL or PRKN, along with the DUB USP30, regulates this process, though specifics remain unclear. The relevance of this process for human disease is also still unclear. Our project aims to decipher the ubiquitin code governing MDV-mediated quality control for mitochondrial import channels and its mechanistic implications. Aim 1 involves defining the ubiquitylation response in MDV formation through genetic approaches inducing TOM complex blockage. Aim 2 seeks to understand how ubiquitylation affects MDV formation by identifying functionally relevant ubiquitylation
targets and manipulating their modification status. Aim 3 investigates the consequences of defective ubiquitin signaling on mitochondrial shape and function, clarifying its role in mitochondrial proteostasis.

Through cellular physiology measurements, genetic tools, and mutagenesis, we aim to uncover the mechanisms underlying MDV-mediated quality control and its impact on mitochondrial function and morphology. This research will provide insights into maintaining mitochondrial health and potential therapeutic targets for mitochondrial disorders.

PhD project: Contributions of ubiquitin signaling to the maintenance of mitochondrial import channels

The project is a collaborative project with the group of Helle Ulrich at the IMB Mainz and is funded within the DFG priority program Integration of mitochondria into the cellular proteostasis network” (SPP 2453). The priority program brings together 15 tandem groups in Germany with a common interest in the integration of mitochondria into the cellular proteostasis network and organizes meetings, summer schools etc. In tandem with the group of Helle Ulrich at the IMB, the Methnerlab will characterize different models for the induction of mitochondrial protein import clogging including an optogenetic model. We will also establish the visualization and quantification of MDVs in different physiological and also pathophysiological conditions. We will ultimately clarify the contributions of ubiquitin signaling to mitochondrial physiology upon clogging of mitochondrial import channels.

If you are interested in this project, please select Methner (Meth) as your group preference in the IPP application platform.

Qualification profile:

Are you an ambitious, young scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start!

All you need is:

• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference

We offer

• Exciting, interdisciplinary projects in a lively international environment, with English as our working language
• Advanced training in scientific techniques and professional skills
• Access to our state-of-the-art Core Facilities and their technical expertise
• Fully funded positions with financing until the completion of your thesis
• A lively community ofmore than 200 PhD students from 44 different countries

For more details on the projects offered and how to apply via our online form, please visit www.imb.de/phd.

The deadline for applications is 17 April 2024. Interviews will take place at IMB in Mainz on 1-3 July 2024.

Starting date: 1 August 2024 – 1 January 2025