EPSRC Centre for Doctoral Training in Chemical Biology: Innovation in Life Sciences

The ICB CDT is training a new generation of PhD graduates in the art of multidisciplinary Chemical Biology research, giving them the exciting opportunity to develop the next generation of molecular tools and technologies for making, measuring, modelling and manipulating molecular interactions in biological systems.

EPSRC Centre for Doctoral Training in Chemical Biology: Innovation in Life Sciences Studentships 2019

Currently Available Studentships at the ICB CDT

Combining Machine Learning, Molecular Dynamics and Membrane Biophysics to identify new therapeutics for the treatment of Tuberculosis

Funded by the CDT in Chemical Biology: Innovation in Life Sciences – 1+3 year PhD studentships - APPLY HERE

Supervisors: Professor Ian GouldDr Nick BrooksProfessor Bernadette Byrne

Tuberculosis (TB) is currently one of the world’s leading causes of mortality with 10 million new cases reported in 2017 alone and 1.3 million deaths (Global Tuberculosis Report 2018 WHO), a further complicating factor is the evolution of multi-drug and totally drug resistant strains. There is an urgent need to develop effective new therapeutic agents to target TB and critical in this process is the identification of a suitable protein to target. MmpL3 is a transmembrane protein which is essential for the replication and viability of bacterial cells and therefore represents a suitable target. The recent determination of the structure of MmpL3 from M. smegmatis (Cell 2019; 176: 636-648) provides the starting point for developing new therapeutic strategies. Molecular Dynamics (MD) simulations will be utilised to construct a model of MmpL3 for M. tuberculosis (Mtb) facilitating investigation of drug-protein interactions, known inhibitors will be modelled at physiological conditions with the protein embedded in a realistic representation of the cell membrane. Validation of the computational model will be achieved through the investigation of the structure and mechanics of model membranes, in which Mtb MmpL3 is embedded, via X-ray diffraction and light microscopy. Identification of the binding modes of know inhibitors to Mtb MmpL3 and known drug resistant mutants will be used as input into Machine Learning (ML) to generate rules to search large compound libraries, in particular the Zinc database, to identify suitable compounds to screen. This project will provide the student with a broad range of skills, computational modelling, machine learning, protein expression and purification and experimental membrane biophysics. 

Gut on a Chip 4.0: next generation models to study gut-microbiome-metabolism interactions

Funded by the CDT in Chemical Biology: Innovation in Life Sciences – 1+3 year PhD studentshipsAPPLY HERE

Supervisors: Prof Gary FrostProf Joshua EdelDr Aylin HanyalogluProf Ed Tate

There is currently no readily accessible and realistic model for human gut signaling. Such a model would need to combine computational modelling with functional readouts in a physiologically relevant setting, in the presence of diverse metabolites and receptors in a dynamic microbiota environment, and under the influence of nutrition. This unsolved technological challenge holds back progress in understanding the roles of metabolite signaling for the treatment of obesity and metabolic disease. The aim of the PhD will be to deliver a new human colon microfluidic technology platform that will enable analysis of gut signaling in a near physiological setting, through a computational and physical model. To achieve this we will deliver a human in vitro colonic microfluidic model, complete with mechanically active bacterial microenvironment and neuronal system. This ambitious aim, which has never been achieved before, requires a highly inter-disciplinary PhD necessitating specialists in 4 main areas in order for the project to progress and succeed: device design and fabrication, GPCR biology, chemical probes, and organoid transfer to the device. Our industrial partner Emulate will play an active role in the PhD.  We are seeking students to have a keen interest in advanced cell models and hands on experimental biology. 

By the end of the PhD the we envisage that the student will have delivered a near human colonic model which can be used to understand the complexed relationship between nutrition, microbiota and multidimensional GPCR signaling pathways.

Next generation Disease Screening using Nanosensors

Funded by the CDT in Chemical Biology: Innovation in Life Sciences – 1+3 year PhD studentships - APPLY HERE

This studentship in the ICB CDT is co-funded with Oxford Nanopore Technologies.

Supervisors: Professor Joshua EdelDr Alex IvanovAndy Heron | Richard Gutierrez | Professor Tony Cass

There is an enormous need for analytical methods that can achieve simultaneous detection of multiple  proteins and miRNA in complex biological fluids. A technology that can achieve this holds the promise of far-reaching impact in multiple healthcare grand challenges ranging from neurodegenerative disease to several major cancers. In a collaboration between Imperial College London and Oxford Nanopore Technologies, this project aims to develop a multiplexed label-free detection strategy for the detection of soluble proteins and miRNA in biofluids.

We have demonstrated proof of principle of using molecular carriers which we showed enables improved selectivity and sensitivity in complex biological solutions. (Nature Communications 2017, Nature Communications 2019).

Within this multidisciplinary project the technology will be further expanded to a panel of key proteins and microRNA sequence linked to major neurodegenerative diseases and cancers which are either up or down regulated in patients. The proposed strategy is universal and if successful this pilot work will build the basis for a general approach for the detection of proteins and small molecules such as miRNA and neurotransmitters in complex unmodified samples. 

 

For more information on the eligibility criterea and how to apply for ICB CDT studentships please visit the ICB CDT website.