New Synthetic Affinity Ligands Based on “Plastic Antibody” Technology as Potential Antisense Agents / Trapping G-tract Oligonucleotides With a Biomimetic Nano-Cage: New Synthetic Affinity Ligands Based on “Plastic Antibody” Technology

New Synthetic Affinity Ligands Based on “Plastic Antibody” Technology as Potential Antisense Agents:
The studentship will explore the potential application of computationally designed polymeric affinity ligands (Plastic Antibodies) as a new type of agent with potential application as a biological tool and also in DNA antisense therapy. Although promising, antisense oligonucleotides suffer from several practical disadvantages such as inherent toxicity, short lifetimes due to enzymatic degradation and low cellular uptake. In order to circumvent some of these, a variety of methods have been proposed, including chemically modified nucleotides (e.g. PNA) and use of delivery vectors (such as virus, lipids, liposomes, peptides, polymers, nanoparticles).
Project Aim: The current project will focus on the development of such vectors as the actual “antisense” element, capable of binding to the sequence of interest without the need for an additional oligonucleotide payload. Recent developments in the automated synthesis of polymeric affinity ligands (Plastic Antibodies) using an immobilised nucleotide approach from the Biotechnology Group means that for the first time a reliable supply of soluble synthetic polymers with pre-determined molecular recognition and sub-nanomolar affinities will be available for testing. The affinity ligands will be developed against DNA sequences involved in regulation gene expression.
Results of this research could lay the foundation for a whole new range of tools for the study of mechanisms involved in cell/disease regulation, as well as potential new therapeutic agents.

Trapping G-tract Oligonucleotides With a Biomimetic Nano-Cage: New Synthetic Affinity Ligands Based on “Plastic Antibody” Technology:
Alternative splicing of RNA is a widespread post-transcriptional mechanism that occurs in higher eukaryotes and is responsible for proteomic diversity. Disruption of the networks involved in the regulation of splicing contributes to several diseases including cancer. G-tract RNA sequences have been implicated in the regulation of these networks. Their mode of action is currently unknown; however they have been proposed to be important for many cellular events, such as telomere maintenance, or transcription initiation. However, there are no examples of synthetic molecules capable of binding to single-stranded G-tract oligonucleotides.
Project Aim: The aim of the project is to synthesise polymeric affinity ligands (Plastic Antibodies) capable of interacting with G-tract oligonucleotides. Recent developments in the automated synthesis of polymeric affinity ligands (Plastic Antibodies) using solid-phase approcah means that for the first time a reliable supply of soluble synthetic polymers with pre-determined molecular recognition and sub-nanomolar affinities will be available for testing. The affinity ligands will be developed against DNA sequences involved in regulation gene expression.
The candidate will receive training in modern methods of polymer synthesis, molecular modelling, molecular imprinting, nanoparticles characterisation, use of biosensor platforms such as QCM and Biacore, oligonucleotide chemistry, mass spectrometry, and HPLC.

We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.