Dr Hanna Kwon
Supervisor Details
Research Interests
Metalloenzyme mechanisms
In the 20th century, X-ray crystallography revealed a molecular world at a level previously unimaginable, far beyond the limits of the microscope. In my research group, we use structural biology techniques including but not limited to X-ray and neutron crystallography, and X-ray free electron laser to understand the mechanisms of metalloenzymes. X-ray crystallography is a powerful tool that gives three dimensional structures at atomic resolution; however, it only provides static pictures. Enzyme reactions are dynamic processes that take place in ultrafast time scale, necessitating the development of new tools and techniques to observe them.
The ultimate goal is to routinely produce “a molecular movie” through time-resolved crystallography utilising rapidly evolving synchrotrons, XFELs and cryoEM to better understand the structural dynamics of biomolecular catalysis.
One of our main research focuses is to understand the catalytic activity and biological function in heme proteins. Heme is essential for the survival of virtually all living systems and has long been recognised as the prosthetic group of the active site in proteins which play significant roles in catalysis, oxygen transport and electron transfer. These are some of life’s most fundamental processes. Our work on heme peroxidases is in collaboration with Professors Peter Moody (University of Leicester), Emma Raven (University of Bristol) and Dr Jon Warrall (University of Essex).
We also utilise neutron crystallography which has the unique power to visualise hydrogen atoms; essential in studying enzyme mechanisms. We collaborate with scientists at Institut Langevin in Grenoble, France and MLZ in Munich, Germany.
Project Details
Dr Kwon is the supervisor on the below project:
Revealing Reactivity in Cancer-Associated Heme Proteins: Novel Time-Resolved Structural Approaches
Secondary Supervisor(s): Dr Philip Ash
University of Registration: University of Leicester
BBSRC Research Themes: Understanding the Rules of Life (Structural Biology)
Apply here!
Deadline: 4 January, 2024
Project Outline
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme involved in the degradation of tryptophan to kynurenine. Cancer cells upregulate IDO1 to escape normal immune responses and, in many cases, a high expression of IDO1 is connected to poor prognosis. Understanding the precise mechanisms by which IDO1 modulates these processes is of paramount importance for therapeutic development and a deeper comprehension of immune homeostasis.
This project aims to investigate the catalytic mechanism and structural dynamics of IDO1 using cutting-edge structural and spectroscopic techniques, and computational analysis. Spectroscopy offers a powerful means to probe the intricate molecular events occurring during IDO1 catalysis in real-time. A combination of X-ray and time-resolved vibrational spectroscopic methods will be used to probe mechanistic details of IDO1. These methods will provide critical data on catalytic timescales that will feed directly into cutting-edge time-resolved structural studies.
The outcomes promise to extend our understanding of this crucial enzyme and its implications in health and disease, with potential far-reaching impacts in immunology and drug discovery.
A PhD student will gain a broad range of interdisciplinary skills in structural biology, chemical biology and biophysics in order to address an important question in cancer biology.
Techniques
- Molecular Biology (cloning & mutagenesis)
- Protein expression and purification (bacterial and mammalian)
- Enzyme kinetics
- Protein crystallisation
- Structure determination
- X-ray Spectroscopy
- Time-resolved spectroscopy (infrared, Raman)
- Synchrotron science
- Chemical synthesis
Dr Kwon is co-supervisor on a project with Dr Philip Ash.