51³Ô¹ÏÍø

Title

Enzymatic Technologies for Discovery of Improved Oligonucleotide-peptide conjugates

This project is co-sponsored by the EPSRC CDT in Chemical Biology and  

Supervisors

• , Department of Chemistry, 51³Ô¹ÏÍø
• , Department of Chemistry, 51³Ô¹ÏÍø
• , Department of Chemistry, 51³Ô¹ÏÍø
• Dr Siddique Amin,
• Dr Samantha Staniland,

Abstract

Modified nucleic acids have emerged as an important class of therapeutic agents and vaccines, which are set to transform the prevention and treatment of many diseases. The three main classes of nucleic acid therapeutics (NAT) are antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs) and modified aptamers. In addition to 18 approved drugs, more than 150 different modified nucleic acid therapeutics are currently in clinical trials for the treatment of cancer, cardiovascular, neurodegenerative and various infectious diseases, as well as other ailments.

Currently two main challenges remain to be addressed around: (i) scalable synthesis of NAT; and (ii) efficient target cellular delivery. The production of modified oligonucleotides relies on solid phase chemical synthesis, which is challenging at the scale required for NAT manufacture. This is beginning to be addressed through the development of new enzymatic methods for modified oligonucleotide assembly, but this technology has a long way to go before it will be industry ready. Oligonucleotide delivery has been partially addressed through the development of lipid nanoparticles, but these lack the necessary selectivity, require relatively high doses, and thus risk off-target toxic effects. Several oligonucleotide-peptide conjugates (OPCs) show promise in clinical trials. However, the assembly of OPCs is synthetically challenging, which can limit the number of constructs/sequences available for screening. 

In this project, we aim to develop new enzymatic technology that will allow vast libraries of OPCs to be assembled and then rapidly screened “direct-to-biology” for highly efficient receptor mediated, tissue specific cellular uptake, increased stability, and improved efficacy in vivo. This opportunity is ideally suited to applicants with interests in chemical biology, drug discovery, nucleic acids, and/or peptide research. Individuals who are keen to work at the chemistry–biology interface in a highly interdisciplinary environment are encouraged to apply. This project is a collaboration between researchers at 51³Ô¹ÏÍø College and AstraZeneca. The successful candidate will benefit from a placement period working in the AstraZeneca labs, and will receive a significantly enhanced stipend of £31,805 pa, which includes additional funding from the .

For further information contact: j.micklefield@imperial.ac.uk

Also see our websites: 

Eligibility

This project is only open to applicants with Home fee status.  For further information, please review our and .

Title

Rewiring cancer targets through proteome-wide discovery of molecular glues

This project is co-sponsored by the EPSRC CDT in Chemical Biology and  

Supervisors

• , Department of Chemistry, 51³Ô¹ÏÍø
• Department of Chemistry, 51³Ô¹ÏÍø
• Dr Iacovos Michaelides,
• Dr Niall Anderson,

Abstract

Molecular glues are redefining what is druggable in biology. By inducing or stabilising protein–protein interactions, they enable selective modulation of targets long considered inaccessible, including transcription factors, chromatin regulators and signalling scaffolds. Unlike conventional inhibitors, molecular glues act by rewiring cellular interaction networks, offering new mechanisms such as degradation, sequestration and transcriptional control. However, their discovery remains largely serendipitous, constrained by the lack of scalable technologies to systematically identify glueable interactions across the proteome.

This project will establish a powerful new platform for molecular glue discovery, combining chemical biology, proteomics and data-driven analysis. Using PRISM (Proteome-wide Recruitment and neo-Interactome Screening for Molecular glues), we will map compound-induced protein–protein interactions directly in complex biological systems, revealing “neo-interactors” that define glueable interaction space. By screening focused libraries derived from existing ligands, the project will repurpose known chemical matter to generate entirely new induced proximity mechanisms and therapeutic hypotheses.

The student will develop and apply high-throughput proteomic workflows to identify and quantify ternary complexes, validate molecular glue activity using orthogonal biophysical and cellular assays, and link induced interactions to functional outcomes in disease-relevant models. The resulting datasets will form a unique resource of glueable protein–protein interactions, enabling machine learning approaches to predict and design molecular glues.

This is a multidisciplinary project at the interface of chemical biology, proteomics and translational drug discovery. It will suit candidates with a strong background in chemistry or chemical biology and an interest in applying quantitative and data-driven approaches to complex biological systems. Training will be provided across 51³Ô¹ÏÍø and AstraZeneca, with opportunities for industrial collaboration and exposure to real-world drug discovery.

The successful candidate will benefit from a significantly enhanced stipend of £31,805 pa, which includes additional funding from the .

Tate group website: /tate-group

Eligibility

This project is only open to applicants with Home fee status.  For further information, please review our and .

Title

Transparent 3D-printed soil: biophysics and metabolomics of root-soil interactions

This project is sponsored by  

Supervisors

• , Department of Life Sciences, 51³Ô¹ÏÍø
• , Department of Materials, 51³Ô¹ÏÍø
• , Department of Life Sciences, 51³Ô¹ÏÍø
• Dr Mark Johnston,
• Dr Giovambattista Depietra,
• , School of Design, Royal College of Art & School of Design Engineering, 51³Ô¹ÏÍø

Abstract

Understanding how soil structure influences plant growth and metabolism at the molecular level is fundamental to agricultural science, yet root systems remain inaccessible to quantitative study in natural soil due to optical opacity and environmental heterogeneity. This project develops transparent, 3D-printed hydrogel substrates that replicate authentic soil pore architecture, enabling direct imaging of root system development coupled with metabolomic profiling under controlled conditions.

Using X-ray micro-computed tomography to characterise real soils under different management practices, this project will translate volumetric data into printable CAD models and fabricate biocompatible substrates via stereolithography. The platform enables systematic investigation of how soil physical structure affects root architecture and metabolite exudation—measurements currently impossible in natural soil or structurally unrealistic transparent substitutes.

The MRes phase establishes the imaging-to-printing pipeline using Arabidopsis; the PhD extends to crop species (wheat, tomato) and agricultural challenges, including chemical treatments, biotic interactions, and abiotic stress.

The project is an interdisciplinary collaboration with Syngenta, integrating X-ray imaging, additive manufacturing, plant biology, and metabolomics, with Syngenta providing agricultural R&D context and imaging expertise.

Keywords: Controlled-environment agriculture; Soil model; X-ray micro-computed tomography; 3D-printed hydrogel; Root imaging; Root system architecture; Plant metabolomics 

Eligibility

This project is only open to applicants with Home fee status.  For further information, please review our and .