Four-stranded DNA structures are important for the regulation of gene expression. Sequences which may be able to adopt such structures have been identified in genes related to human health and disease. This project is to characterise these sequences to determine If they present new potential drug targets.
Department: Pharmacy
Supervised by: Dr James Hall & Dr John Brazier
DNA is most commonly thought of as a double-helix structure. However, higher-order multi-stranded forms of DNA exist within nature and are of significant interest to the scientific community. DNA G-quadruplexes and I-motifs are examples of higher-order DNA structures which adopt a four-stranded assembly, from G and C rich sequences respectively. These structural forms of DNA are thought to play a role in the regulation of gene expression and have been visualised within cells, forming in different numbers during the cell cycle. Over the previous several years, a series of ongoing theoretical projects led by the UROP supervisors have identified potential G-quadruplex and i-motif forming sequences in the promotor regions of genes implicated in human health and disease. This Includes genes Implicated In conditions Including: 1. Breast cancer 2. Bipolar disorder 3. Alzheimer's disease 4. Pancreatic cancer These sequences may be accessible as potential new drug targets, which could be targeted by small-molecule ligands, or contribute to the gene regulatory processes. The two students working within this project will characterise these Identified sequences in solution under a range of biologically relevant conditions, to examine whether they do actually form the structures of interest and establish key factors, such as their thermal stability. Students will also set up crystallization experiments for X-ray diffraction. The final area(s) In which each student works will be mutually agreed between the student and supervisors meaning that the project can be tailored to the interests of the individual students.
Preparation of stock solutions of oligonucleotides at known concentration. Preparation of oligonucleotide solutions under different conditions, including changing pH and salt composition. Measurement of temperature dependent UV spectra. Calculation of thermal melting transitions Preparation of crystallisation plates
The student will need to have prior experience within a chemical or biological laboratory environment. Examples of suitable programmes of study include, but are not limited to, biological/biomedical sciences, biochemistry, chemistry-focussed programmes and healthcare programmes with a significant laboratory component, including Pharmacology, Pharmacy and MPAS.
The student will further develop their laboratory skills within a practical lab environment at the biology/chemistry interface. They will develop skills in the analysis of biological molecules and in analysis techniques, including UV/visible absorption spectroscopy. Students will also develop evaluation skills through the analysis of relevant spectroscopic data and also improve their presentation skills, with an oral presentation to summarise their findings due to take place in the final week (along with the UROP poster presentation).
Chemistry & Pharmacy Building, Whiteknights Campus, UoR
9-5, Mon-Fri
Monday 13 June 2022 - Friday 22 July 2022
The post will be advertised centrally on the UROP website between 21st February and 4th April 2022. Students should submit their CV and Cover Letter directly to the Project Supervisor (click on supervisor name at the top of the page for email). Successful candidates will be invited for an interview.