Post-doc position at IST Austria: deciphering the structural and dynamical basis of allosteric enzymes by NMR

Post-doc position in the Schanda group at IST Austria: deciphering the structural and dynamical basis of allosteric enzymes

 

The project

What is the mechanistic basis for long-range communication in allosteric proteins? And how, along evolution, did proteins acquire the capacity to be allosterically regulated?

We study these questions with an integrated approach that combines state-of-the-art NMR approaches, both in solution and in the solid state, with a host of biophysical methods, simulations and functional assays. The family of proteins we study are large (>120 kDa) and we have successfully established functional and dynamical studies of several such large machineries at the atomic level.

A success of the project is when we will understand what are the structural and dynamical events that enable allosteric communication, and what it is that makes the non-allosteric proteins of this family behave differently. We will characterise dynamics on multiple time scales and characterise short-lived states and their role for allostery and enzymatic function.

The proteins we study are generally considered rather challenging due to their size. Building upon several successful cases from our group, we will overcome these challenges by several approaches. We have available several ways of getting specific isotope labels in strategic positions in otherwise deuterated proteins (including yet unpublished ones); these methods provide high resolution even in solution-NMR despite the protein size. Moreover, we use magic-angle spinning NMR to gain access to essentially all atoms, independent of the size. Specific labelling also helps there, as it supports the precise determination of dynamics.

In this particular project, we will combine these techniques with high-pressure NMR, thereby characterising how pressure activates proteins of organisms living in the deep sea. Together with other proteins, mesophilic or thermophilic, we will build an understanding of the crucial elements that make proteins allosteric or non-allosteric, including the activation of the allosteric capacity.

 

Requirements

Successful candidates shall have a PhD degree in biochemistry or biophysics, and ideally experience in NMR spectroscopy applied to biomolecules. A strong background in structural biology and protein production and/or bio-NMR methods development is expected.

We expect candidates to enjoy creative and critical thinking, possess a strong motivation to learn new techniques, solve puzzling questions, and overcome technical challenges. We are a small international team and we look forward to working with a team player who is eager to take responsibility for their project and genuine interest in the group’s work.

We are aware that most candidates will not have experience in all aspects, from MAS NMR to solution- (& pressure-) NMR to biochemistry, and we expect a strong dedication to learning and acquiring new skills of use for this project and the further career.

 

The environment we offer

Our group is located at IST Austria, at the outskirts of Vienna, one of the cities with highest quality of life according to many rankings. The group was established at ISTA in 2021, and we currently have 9 members from 7 different countries. English is the institute language.

We have access to three brand-new spectrometers (600, 700 and 800 MHz + soon a 400), equipped with either solution-state cryoprobes or MAS NMR probes (0.7 mm to 3.2 mm). We furthermore have access to a state-of-the-art cryo-EM facility and various techniques for protein production and characterisation.

Our institute is rapidly growing, and you will have the chance to be exposed to a wide range of research areas (with many joint seminars), and with several new faculty joining our structural biology programme in 2024, you will have a chance to connect to a community including cryo-EM, electron tomography, machine learning, protein design, many groups working in developmental, cellular and molecular biology,… We believe it is a highly stimulating environment for a young researcher on an academic career track.

 

The post-doc contract can be up to 5 years, allowing candidates to develop not only their skills but also prepare for positioning themselves on their way to an academic career.

 

How to apply:

Please send your appliction, including

* a detailed letter that describes your background and motivations/reasons for applying as well as your vision for your research, for your postdoc period and beyond,

* your publication record, possibly your experience in supervision of students, presentations,…; ideally complement this by stating what it is that you are particularly proud of,

* names of 2-3 references

to paul.schanda@ist.ac.at

 

Relevant publications from our group:

Dynamics in large assemblies

Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR Nature Communications. 2022, 13: 1927, https://www.nature.com/articles/s41467-022-29423-0  

Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR J. Am. Chem. Soc. 145 (19), 10700-10711 https://pubs.acs.org/doi/10.1021/jacs.3c01200

Mechanism of the allosteric activation of the ClpP protease machinery by active-site inhibitors. Science Advances, 5 (9), eaaw3818 https://advances.sciencemag.org/content/5/9/eaaw3818

 

MAS NMR methods development & dynamics studies

The rigid core and flexible surface of amyloid fibrils probed by magic-angle spinning NMR of aromatic residues Angew. Chem. Int. Ed. 2023, e202219314. https://doi.org/10.1002/anie.202219314

Aromatic ring dynamics and excited states detected in a half-megadalton aminopeptidase by specific labeling and MAS NMR J. Am. Chem. Soc.141 (28), 11183–11195 https://pubs.acs.org/doi/10.1021/jacs.9b04219; highlighted in: https://f1000.com/prime/735988056#eval793563211

Review: Protein dynamics detected by magic-angle spinning relaxation dispersion NMR Current Opinion in Structural Biology 82, 102660 https://doi.org/10.1016/j.sbi.2023.102660

Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex Nature Communications. (2019), 10(1):2697. https://www.nature.com/articles/s41467-019-10490-9

 

Chaperones & mitochondria

Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell 175(5): 1365-1379 https://www.cell.com/cell/fulltext/S0092-8674(18)31395-3; highlighted in  https://f1000.com/prime/734441988

Architecture and assembly dynamics of the essential mitochondrial chaperone complex TIM9·10·12. Structure2021, 29: 1-9. https://doi.org/10.1016/j.str.2021.04.009

Structural basis of client specificity in mitochondrial membrane-protein chaperones., Science Advances. 2020, 6, 51: eabd0263 , https://advances.sciencemag.org/content/6/51/eabd0263

Structural Investigation of a 1 MDa Chaperonin in Action. Science Advances, 4, eaau4196 http://advances.sciencemag.org/content/4/9/eaau4196.full

 

 

Find more information here:

The Schanda group: https://ist.ac.at/en/research/schanda-group/

Publications: https://scholar.google.com/citations?hl=en&user=peo3k9EAAAAJ&view_op=list_works&sortby=pubdate

Biochemistry & structural biology at IST Austria: https://biochemistry.pages.ist.ac.at/

Facilities at ISTA: https://ista.ac.at/en/research/scientific-service-units/

NMR facilty at ISTA: https://ist.ac.at/en/research/scientific-service-units/nuclear-magnetic-resonance-facility/#Services

Paul Schanda

Institute of Science and Technology Austria

Office: Sunstone I23.O1.009

____________________________

https://ist.ac.at/en/research/schanda-group/