List of Projects of the 2020 cohort

Here is a list of the studentships starting in autumn 2020 and that will form our second cohort of the CDT in Chemical Biology: Innovation in Life Sciences.

Studentships are now open for applications, note that there will be further studentships announced with our industrial partners in a few weeks to come.

CDT Studentships

Ultrasensitive prostate cancer screening based on miRNA sensing from whole blood

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

Prof Joshua Edel |Dr Sylvain LadameDr Alex IvanovProf Charlotte Bevan

Current tests for the diagnosis, prognosis and stratification of prostate cancer suffer from two main drawbacks, being either invasive (requiring tissue biopsies) or inaccurate and therefore unreliable. Recent studies have highlighted the potential of microRNA (miRNA) as a minimally-invasive diagnostic and prognostic biomarker for various cancer types, including prostate. The main challenges with current miRNA sensing strategies relate to the naturally low abundance of these biomarkers in bodily fluids and high sequence homology between fragments. Besides, most technologies available to date cannot detect such biomarkers directly from whole blood and require heavy sample processing, which in the absence of standardised protocols can be a major source of error. While miRNAs have been reported as promising diagnostic biomarkers for prostate cancer, the lack of technologies enabling their direct and accurate detection from blood has prevented their broader use in new screening tests. As part of this project, we propose to improve diagnostic specificity beyond the PSA test by performing multiplexed detection of up to 5 miRNA biomarkers. This innovative technology has the potential to enable new blood tests for prostate cancer and future point-of-care devices, decreasing diagnostic uncertainty and improving quality of life.

Smart Bioisosteres: Beyond a spatial mimic to improved plant biology

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

Dr James Bull | Dr James MurrayBill Whittingham 

Bioisosteres are essential alternative design options in the development of new agrochemicals, to retain or improve overall biological properties of an active ingredient, such as activity, biokinetics, and metabolic stability. However, the development of bioisosteric replacements for linking groups (not directly involved in binding to the protein target) has to date focused exclusively on their scaffolding properties, to mimic topology, and neglected the effect on the properties of the substituents directly attached to the scaffold (e.g. pKa or H-bonding potential, hybridisation). In developing new agrochemicals, these substituent features are crucial to the progress of a compound, and notably the potential to reach the relevant site of activity. This project will design, synthesise and assess new bioisosteres. It will examine the change in the physicochemical and ADME properties the bioisosteres can confer to a compound as a whole (logP, solubility, metabolic stability), as well as the particular changes to the key functional substituents on the scaffold, providing new insights to these materials.

Advantageous scaffolds will be incorporated into known agrochemical compounds for further investigation including in vitro enzyme assays, whole plant studies and X-ray studies.

The project would suit a candidate with experience in synthetic chemistry and interests in the application to plant chemical biology.

Compartmentalised biomembrane capsules as novel vaccine technologies

Supervisors

Yuval Elani and Oscar Ces

Project description

The development of new vaccine technologies that are targeted, effective, and programmable is increasingly being recognised as one of the key industrial challenges in chemical biology. The packing of vaccines , both protein- and RNA-based, inside a lipid-bound compartment is currently at the forefront of approaches to a more effective delivery mode of the active agents.  The majority of vaccine delivery vehicles share a common structural motif, namely that of a single compartment encased by a lipid layer; this lack of architectural diversity has hindered their technological potential.

We know from biology that step changes in sophistication of chemical microsystems can be achieved by having non-uniform spatial organisation; this is achieved through compartmentalisation of content in discrete spatial locations. In this project, novel vaccine delivery vehicles will be developed using microfluidic technologies, where the size, membrane composition, encapsulated cargo, and number of compartments can be ‘dialled-in’ on demand. To do this, the student will develop underlying microfluidic platforms for the layer-by-layer assembly of a suite of lipid membrane motifs using a molecular assembly line. The ability of these structures to house both the antigen and adjuvant in different compartments will be explored, together with their potential for multi-stage release of a vaccine payload.  The project would suit a candidate with a background in Chemistry, Chemical Engineering, Bioengineering and related disciplines.

For more information please contact Dr Yuval Elani: y.elani@imperial.ac.uk

Leverhulme 2020

Unlocking a new toolkit for mediating protein-based interactions between synthetic cells and real cells

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics – 3 year PhD studentships - APPLY HERE

Supervisors: Dr Rudiger Woscholski Prof Oscar Ces

A major bottleneck in the field of cellular bionics and bottom-up synthetic biology is the ability to decorate and functionalise the chassis of synthetic cells with user defined proteins. Unlocking this technology bottleneck would transform our ability to mediate interactions between synthetic cells and between synthetic cells and real cells across extended length scales including tissues based materials. This project will lead to the development of a new generation of artificial lipids that are able to reversibly bind proteins thereby revolutionising our ability to functionalise cellular bionic systems. We will validate this strategy by using this approach to modulate communication between synthetic cells and real cells at the single cell level. In addition by making use of extracellular proteins we will manufacture hybrid tissues that accommodate living and synthetic cells.