The main scientific themes in our group are centred on the elucidation of the molecular and supramolecular recognition of biomacromolecules with synthetic ligands and natural proteins. Below are listed three representative projects that are currently being developed:
Ligands binding to RNA quadruplexes to control gene expression. In this project, we are exploring the hypothesis that intramolecular RNA G- quadruplexes regulate gene expression at the translational level. Indeed, the formation by an mRNA of a stabilized G-quadruplex type structure could either inhibit or prevent the translation process and repress gene expression. The general strategy consists in the synthesis of hybrid molecules of general structure PNA1-Heterocycle-PNA2 where Heterocycle and PNA1,2 are predicted to recognise the quadruplex structure and the two flanking single stranded RNAs respectively.
Functional interaction between PARP-1 and promoter DNA quadruplexes. The specific aim is to demonstrate that PARP-1 regulates the expression of certain genes at the transcriptional level via specific interactions with DNA quadruplexes located within the promoter region of these genes. Our study will focus on the interaction of the zinc finger DNA binding motif of PARP-1 with the promoters of the inducible Nitric Oxide Synthase (iNOS) and pS2 genes in which we have identified two putative DNA-quadruplex forming sequences.
Fluorescent chemosensors using dynamic covalent chemistry. Fluorescent chemosensors are dye molecules whose fluorescence changes through specific molecular recognition events. The aim of this project is to create new cyanine-dye inspired chemosensors consisting of two non fluorescent entities capable of interacting with each other via reversible covalent bond formation upon binding to specific metabolites, interaction resulting in the emission of a fluorescent signal.