Dr Anastasia Zhuravleva
- Position: Lecturer
- Areas of expertise: biological NMR; structural biology; biophysics; molecular chaperones; protein folding; protein quality control; protein-protein interactions
- Email: A.Zhuravleva@leeds.ac.uk
- Location: 6.01 Miall
I am an experimental structural biologist with a strong interest in mechanistic understanding of multicomponent protein systems and elucidation of molecular mechanisms underlying signal transduction inside the cell. My main research interest is focused on the mechanistic characterization of the protein quality control (PQC) system in the endoplasmic reticulum (ER); as well as the understanding of intriguing relationships between alterations in local ER environment, conformational variability of the individual components of the PQC system and real-time functional adjustments of the entire PQC network. My group is currently funded through BBSRC New Investigator Scheme and EPSRC First Grant.
I obtained a masters degree with honors in Chemistry and Material Science in 2002 from the Moscow State University. In 2002, I joined the groups of Prof Orekhov and Prof Billeter at the Swedish NMR Centre (University of Gothenburg) as a graduate student. I used bimolecular NMR to elucidate of the role of protein conformational dynamics in protein functions and signal transduction. In 2006, I continued my studies in biomolecular NMR as a postdoctoral fellow in the group of Prof Skrynnikov (Purdue University, USA). In 2007, I joined the group of Prof Gierasch, who is an expert in protein folding and molecular chaperones. My main research project aimed at the understanding of molecular allostery in the Hsp70 chaperone family. In July 2013, I was recruited to Leeds as a lecturer in biological NMR.
Life and Death Dilemma: Molecular Mechanisms of the UPR
Nearly one-third of all newly synthesized proteins (including the majority of secreted and membrane proteins) are first segregated in the endoplasmic reticulum (ER) – the organelle responsible for proper folding and posttranslational modifications for these proteins. Imbalances in ER folding homeostasis results in many pathological processes, including neurodegenerative diseases, diabetes and cancer. A conserved protein quality control (PQC) network of ER molecular chaperones and degradation enzymes controls correct protein folding and the disaggregation/clearance of misfolding proteins. To this end, two key PQC players – the ER Hsp70 molecular chaperone called BiP and the ER stress sensor Ire1 – are very attractive pharmaceutical targets for tackling protein-folding diseases. Our group utilizes a multidisciplinary cutting-edge approach that combines biomolecular nuclear magnetic resonance (NMR), mass spectrometry (MS) and other biophysical approaches (calorimetry, fluorescence), computational modelling and simulations, and protein construct design to obtain mechanistic understanding of how the interplay between Ire1 and BiP affects cell fate in health and disease. Our long-term goal is to develop a realistic model that are able to recapitulate key aspects of the unfolded protein response (UPR) in human cells and tissues and quantitatively predict how different physiological and pathological alterations along signalling cascades impact cellular homeostasis and disease progression.
Allosteric posttranslational fine-tuning of chaperone activity
Growing evidence suggests that the remarkable cellular ability to adjust folding capacity relies on post-translational fine-tuning of molecular chaperones such as Hsp70s. Our research addresses two of the most fundamental questions: i) How does fine-tuning of the Hsp70 functional cycle through its posttranslational modifications and interactions with co-chaperones affect Hsp70 ability to assist protein folding. ii) Do protein clients themselves enable customisation of thermodynamic and kinetic parameters of the Hsp70 chaperone cycle for clients’ specific folding needs? We aim to obtain detailed mechanistic understanding of how Hsp70-assisted protein folding can be controlled and fine-tuned by the cellular environment. Our long-term goal is to facilitate future drug developments that enable specific fine-tuning of this fascinating chaperone system.
Development of novel approaches in structural biology to study challenging biomedical systems
We combines the latest developments in fast acquisition methods for solution nuclear magnetic resonance (NMR) to develop a cost- and time-efficient high-resolution hydrogen/deuterium exchange (HDX) approach for structural and dynamic characterization of large protein systems, inaccessible via other structural methods such as X-ray, cryo-EM, and traditional NMR and HDX.Our aim is to develop a novel structural biology approach that enables: i) detailed characterization of large multicomponent systems, including multidomain proteins, transient protein-protein complexes and oligomers; ii) elucidation of conformational transitions in membrane bound proteins; iii) characterization of conformational variability of extended intrinsically disordered regions.In a long term, our goal is to provide new opportunities for elucidation of molecular mechanisms of action for large, multicomponent biological machines and facilitate future drug design for such challenging systems.<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>
- Astbury Centre for Structural Molecular Biology (ACSMB)
I teach undegraduate and graduate biochemistry students;
I am involved in management and assesments of undegraduate and graduate modules.<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://phd.leeds.ac.uk">research opportunities</a> allow you to search for projects and scholarships.</p>
<li><a href="//phd.leeds.ac.uk/project/1404-breaking-the-chaperone-code:-how-do-post-translational-modifications-regulate-hsp70-stress-response?">Breaking the Chaperone Code: How do post-translational modifications regulate Hsp70 stress response?</a></li>