PhD position (Ageing & Disease, Bioinformatics & Computational Biology): Elucidation of the molecular mechanisms regulating protein homeostasis by liquid-liquid phase separation

Thinking of doing your PhD in Molecular Biology? The International PhD Programme (IPP) on Gene Regulation, Epigenetics & Genome Stability is offering talented, young scientists the chance to work at the cutting edge of research. The IPP is 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.

The programme is coordinated by the Institute of Molecular Biology (IMB) — a modern research centre located on the bustling campus of Mainz University in Germany. With a population of 200,000, of which about 40,000 are students, the city of Mainz is charming and open-minded and is within easy reach of cosmopolitan Frankfurt, the Rhine valley region with its castles, vineyards, and nature reserves, and the equally picturesque cities of Wiesbaden and Heidelberg. With Frankfurt airport – the largest airport in mainland Europe – only 20 minutes away, countless European and overseas destinations are within easy reach.

Activities and responsibilities:

In the field of “Ageing & Disease”and “Bioinformatics & Computational Biology”, the IPP research group of Dr Katja Luck offers the following PhD project:

Elucidation of the molecular mechanisms regulating protein homeostasis by liquid-liquid phase separation

Keeping the proteome of a cell under control, i.e. maintaining proteostasis, is essential for a cell and organism to survive. In response to stress, cellular signaling networks need to rapidly adapt and selected as well as misfolded proteins be rapidly and selectively degraded. It has been shown that in response to stress, molecular components such as protein, RNA, and DNA, form membraneless compartments, seen as droplets, foci or bodies under the microscope, by means of liquid-liquid phase separation. These membraneless compartments, some of which are known as cytoplasmic stress granules or nuclear PML bodies, sequester selected proteins and RNA during times of stress, which are released again upon return to physiological conditions. Perturbation of these liquid phase separation processes, i.e. by mutations or other alterations, have been found to lead to aggregation and are linked to neurodegenerative diseases and aging. More recently, phase separation has been shown to also mediate the assembly of nuclear membraneless compartments that recruit the proteasome and drive targeted degradation of proteins in response to proteotoxic stress. The mechanisms of phase separation and proteasome recruitment, which proteins are recruited and subsequently degraded by these compartments, and how these processes differ based on the type of proteotoxic stress remain largely unclear.

PhD project

In collaboration with the Beli lab we aim to employ a systematic, data-driven approach to elucidate the molecular mechanisms that regulate phase separation, proteasome recruitment, and substrate recognition under various conditions of proteotoxic stress. To this end, we will apply a variety of experimental techniques such as siRNA screening, TurboID-MS, Bioluminescence Resonance Energy Transfer, and site-directed mutagenesis as well computational tools for data analysis and integration, and the prediction of protein interaction interfaces. We will also exploit resources of human genetic variants to identify mutations that negatively interfere with the elucidated molecular mechanisms and thus might underlie disease.

You will join a young, highly dynamic, and interdisciplinary research lab. You should ideally have basic expertise in programming and statistics as well as in molecular biology techniques and a strong interest in integrative, data-driven systems approaches to biology.

What we offer:

• Exciting, interdisciplinary projects in a fully 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 of more than 140 PhD students from 40 different countries

Requirements:

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

We seek enthusiastic candidates with a special interest in the following topics:

• Ageing & Disease
• Bioinformatics & Computational Biology
• DNA Repair & Genome Stability
• Epigenetics & Nuclear Dynamics
• Gene Regulation & Evolution
• RNA Biology

Further requirements:

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

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 27 November 2020. Interviews will take place in Mainz on 25-27 January 2021 if the pandemic situation allows. Otherwise we will inform selected candidates in due time about an alternative online programme.

Starting date: 1 March 2021 – 1 September 2021