PhD Positions: Integrated Structural Biology to Decipher Mechanisms of Mitochondrial Protein Import and Allosteric Proteins
Are you fascinated by the link between protein dynamics and biological function? Join our team to explore this connection using atomic-level insights from NMR spectroscopy alongside advanced structural (cryo-EM), biophysical, and biochemical methods. Are you rather particularly interested in pushing methods in NMR methods and/or isotope-labelling? Work with us to develop methodology to get the best of NMR for probing dynamics.
We have several open projects:
- Mitochondrial protein import. We investigate proteins transporting other proteins into mitochondria, across membranes, and into the membrane. We study dynamic interactions between chaperones, receptor proteins, membrane-protein insertases, and potentially disordered proteins in transit. NMR spectroscopy reveals structures, interactions, and dynamics—even in highly disordered systems. Using tailored isotope labeling, solution-state NMR, and solid-state NMR, we overcome limitations to gain comprehensive mechanistic insights.
- The mechanistic basis of allostery and its evolution.Allosteric proteins use complex intramolecular and inter-subunit interaction networks to regulate biological function over long molecular length scales. Dynamics is often central to this communication pathways. We study allostery across a family of enzymes of which some - but not all - are allosteric. This provides us a great opportunity to understand what it takes a protein to be allosteric, and how it evolved, and how it adapted to extreme conditions. We use solution-state NMR (including at high-pressure to understand how allostery works in the deep sea!), solid-state NMR, and combine it with cryo-EM, MD simulations, crystallography,...
- New NMR methods. We develop new ways of getting the best possible NMR data. We combine advanced isotope labelling with new pulse sequences and machine-learning-based analyses.
Our lab is a great fit for you if you:
- Have a solid background in biochemistry, molecular biology, or protein production, or good biomolecular NMR skills
- Are deeply interested in structural biology.
- Have programming skills (not mandatory, but they’re a big plus).
- Bring experience with structural-biology techniques, molecular dynamics simulations, or other biophysical methods (welcome but not required).
- Machine-learning knowledge? Great, we have ongoing projects where we develop ML for NMR.
What we offer:
We are a diverse, international team that values curiosity, creativity, respect, and a collaborative work environment where every member has the opportunity to learn and grow.
Our group is based at IST Austria, just outside Vienna—a city consistently ranked among the world’s most livable. At IST Austria, English is the working language. We have access to state-of-the-art facilities, including:
- Brand-new NMR spectrometers (400, 600, 700, and 800 MHz) with solution-state cryoprobes or MAS NMR probes.
- Cutting edge facilities, including cryo-EM, imaging computation,...
- Extensive resources for protein production and characterization.
As part of ISTA’s rapidly growing research community, you’ll benefit from a rich, interdisciplinary environment. You’ll have opportunities to connect with experts in cryo-EM, electron tomography, machine learning, protein design, developmental biology, and more. Weekly joint seminars and collaborative projects make it an ideal setting for a young researcher aiming for an academic career.
Graduate School Program
You will join ISTA’s Graduate School program, which offers:
- Rotations in other research groups to broaden your expertise.
- A medium-sized, collegial cohort of fellow PhD students.
- A supportive academic and social environment throughout your PhD journey.
Interested?
Apply by January 8 at https://phd.pages.ista.ac.at/phd-application-admission/.
Have questions? Feel free to reach out—I’ll respond as quickly as I can!
Relevant papers from previous PhD students of the group
Chaperones & mitochondrial import
Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space.
https://www.cell.com/cell/fulltext/S0092-8674(18)31395-3
Architecture and assembly dynamics of the essential mitochondrial chaperone complex TIM9·10·12.
https://doi.org/10.1016/j.str.2021.04.009
Structural basis of client specificity in mitochondrial membrane-protein chaperones.
https://advances.sciencemag.org/content/6/51/eabd0263
Structural Investigation of a 1 MDa Chaperonin in Action.
http://advances.sciencemag.org/content/4/9/eaau4196.full
Dynamics in large assemblies
Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR
https://www.nature.com/articles/s41467-022-29423-0
Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR
https://pubs.acs.org/doi/10.1021/jacs.3c01200
Mechanism of the allosteric activation of the ClpP protease machinery by active-site inhibitors.
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. 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 https://pubs.acs.org/doi/10.1021/jacs.9b04219
Review: Protein dynamics detected by magic-angle spinning relaxation dispersion NMR
https://doi.org/10.1016/j.sbi.2023.102660
Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex.https://www.nature.com/articles/s41467-019-10490-9
Find more information here:
our 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/
IST Austria’s PhD programme: https://phd.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