Offer: Post-doctoral researcher - Laboratory of Protein Biochemistry

JOB OFFER

Position in the project: 

Post-doctoral researcher

Scientific discipline:

Molecular biology and biochemistry

Job type:

Full-time position, employment contract

Number of job offers: 

1

Remuneration/stipend amount/month:

Expected gross  salary approx. 11 600 PLN

Position starts on: 

February, 2025

Maximum  period of contract/stipend agreement:

47 months

Institution:

Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland

Project leader:

Krzysztof Liberek

Project title:

Chaperone machinery in protein refolding from amorphous and fibrillar aggregates

Project is carried out within the OPUS 27 grant scheme financed by National Science Centre, Poland

Project description:

Molecular crowding and rapidly changing environmental conditions disrupt the folding of newly synthesized polypeptides and promote the loss of native protein conformation. These disruptions not only deplete functional proteins but also lead to protein aggregation, a significant cellular problem. A special class of proteins known as molecular chaperones has evolved to counteract this process.

In our grant application, we will focus on the mechanisms by which Hsp70 chaperone and its co-chaperones-J-domain proteins (JDP) and nucleotide exchange factors (NEF)- alongside Hsp100 disaggregase, act on protein aggregates to liberate and refold the polypeptides trapped within them. Our comprehensive investigation of the mechanistic aspects of JDP and NEF co-chaperones aims to enhance our understanding of the Hsp70 system, which is the central regulator of protein homeostasis. Specifically, we will examine the role of Class B J-domain proteins in formation of Hsp70 clusters on aggregates. Our preliminary results suggest that Class B J-domain proteins recruit Hsp70 to aggregates in a catalytic-like manner. This proposed mode of Hsp70 loading on aggregates is novel.

Additionally, we will analyze the mechanism of nucleotide exchange factors in substrate disaggregation. An intriguing paradox we aim to address is why NEFs, whose principal role in the Hsp70 cycle is to trigger substrate release, support Hsp70 binding to an aggregated protein and inhibit the folding of single polypeptide chains released from aggregates in the Hsp70-dependent reaction. Furthermore, we will investigate the role of Hsp100 disaggregase in the final folding of disaggregated substrates. Recent studies indicate that Hsp70 alone can generate pulling forces comparable to Hsp100, which raises the question: is the disentangling of polypeptides from aggregates truly the primary role of Hsp100 disaggregase, or is it more crucial for polypeptide folding into native structure?

The main research methodology involves reconstituting the disaggregation system using purified chaperones. We will select proteins whose native conformation can be easily monitored through fluorescence or their enzymatic activity as disaggregation substrates. Our research will utilize several variants of yeast and human chaperone proteins. By analyzing their activities in combination with structural insights, we aim to elucidate their mechanisms and cellular functions, as well as details of their co-operation in refolding of aggregated proteins.

 We will apply several advanced experimental techniques in our research, such as bio-layer interferometry, thermophoresis, surface plasmon resonance, fluorescence measurements, electron microscopy, atomic force microscopy, and various other methods.

Key responsibilities include:

1. performing research using biochemical, genetic and molecular biology techniques (independently and in collaboration with other team members)

2. participation in design of experiments and data analysis

3. participation in preparation and writing of manuscripts

4. supervising younger researchers (PhD students and Master students) involved
   in the project

5. active participation in lab meetings, departmental seminars and conferences

Profile of candidates/requirements:

1. Doctoral degree in biochemistry or molecular biology or biology obtained in 2018 or later

2. Publication record and experimental training in biochemistry and molecular biology. Publications in the field of chaperones are preferable 

3. Ability to communicate fluently in English (spoken and written)

4. Strong motivation to pursue scientific questions, creativity and analytical thinking

5. Research experience (publication proven) in protein purification, protein-protein interactions analysis, enzymatic activities analysis and genetics.

Required documents:

1. Motivation letter (in English)

2. CV (in English)

3. Recommendation letter preferable from the PhD project supervisor and name and email of additional scientist/ supervisor willing to submit references on request.

4. PhD diploma

We offer:

-work in active research team in an excellent international scientific environment
-comprehensive cross-disciplinary training in molecular biology, biochemistry and protein structure/function predictions
-participation in scientific seminars and conferences

Please submit the following documents to:

krzysztof.liberek@ug.edu.pl

Application deadline:

10.01.2025

For more details about the position please visit:

https://en.biotech.ug.edu.pl/research/research_groups/laboratory_protein_biochemistry

Euraxess job/stipend offer: