PhD Position: Maintaining Proteostasis in Aging (m/f/d)

The research group of Anton Khmelinskii in collaboration with Jan Padeken offers the following PhD project:
The progressive deterioration of protein homeostasis (proteostasis) is a primary hallmark of aging. As organisms age, the functionality of the proteostasis network, comprised of molecular chaperones, the ubiquitin-proteasome system and autophagy, declines, leading to the accumulation of misfolded and aggregated proteins that compromise cellular viability. Proteostatic decline is not merely a consequence of aging but an early, causal event whereby loss of proteostasis precedes and predicts organismal decline, and its onset is sufficient to accelerate aging. Conversely, genetic or pharmacological enhancement of proteostasis network capacity can extend lifespan and suppresses age-related disease associated with protein misfolding across multiple model systems. These observations raise fundamental questions: what endogenous small molecules sustain proteostasis during aging, can their supplementation prevent neurodegenerative (and other protein folding diseases) and slow the aging process?

PhD project: Therapeutic applications of small molecule modulators of proteostasis

Organisms across all domains of life employ the accumulation of small organic osmolytes, which include molecules such as betaine and taurine, to mitigate proteotoxic stress. Recent work has also demonstrated anti-aging properties of this molecules, through yet unclear mechanisms. This project aims at dissecting the mode of action of different osmolytes using human cellular model systems and C. elegans as a model of organismal aging. We would like to address the following questions:

1. How do osmolytes affect cellular and organismal physiology?
2. Which types of stresses can be mitigated with exogenous osmolytes?
3. What types of protein misfolding pathologies (e.g., neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimers's, Parkinson's, Huntington's) can be ameliorated with exogenous osmolytes?

The project is part of an ongoing collaboration between the Khmelinskii and Padeken groups, which gives you the opportunity to become an expert in a wide range of methods and experimental approaches. This includes transcriptomics, proteomics, cell and molecular biology, fluorescence microscopy and advanced high-throughput mutagenesis screening.

If you are interested in this project, please select Khmelinskii/Padeken as your group preference in the IPP application platform.

Are you an ambitious 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

• 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 the online form using the apply button.

The deadline for applications is 15 October 2026. Interviews will take place at IMB in Mainz on 18+19 January 2027.
Starting date: 1 February - 31 July 2027