Revealing Reactivity in Cancer-Associated Heme Proteins: Novel Time-Resolved Structural Approaches


   Molecular and Cell Biology

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  Dr Hanna Kwon, Dr Philip Ash  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

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 that will be undertaken during the project

·        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 

Enquiries

Project Enquiries to [Email Address Removed]

Programme enquiries to [Email Address Removed]

To apply please refer to

https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp


Biological Sciences (4)

Funding Notes

All MIBTP students will be provided with a 4 year studentship.
This includes:
Tuition fees at the UK fee rate*
a tax free stipend which for 2023/4 is £18,622 (2024/25 stipend to be confirmed)
a travel allowance in year 1
a travel/conference budget
a generous consumables budget
use of a laptop for the duration of the programme.
The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.