Diagnoses of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Motor Neuron Diseases, and Multiple Sclerosis are increasing globally due, in part, to increases in life expectancy and aging. Within these diseases, protein structural changes in the brain and CNS have been identified and are thought to be major contributing factors. In particular, increased levels of phosphorylation of serine residues within CNS proteins (e.g., Tau and β-synuclein proteins) have been identified. This phosphoserine post-translational modification (PTM) might then undergo reactions to generate reactive intermediates within the protein structure. Such reactive intermediates within proteins are known to undergo irreversible reactions which could lead to overall protein misfolding and ultimately aggregate formation, which is clinically observed in many important neurodegenerative diseases.
This project aims to study this possibility by designing clinically relevant phosphoserine-containing peptide fragments, using a range of computational biology methods (protein modelling, molecular dynamics), and synthesising the designed peptides using solid-phase methods. Stability studies under physiological conditions (pH, temperature, metal ions, etc.) to measure formation of reactive intermediates and crosslinking reactions will be undertaken, using a range of analytical and spectroscopic methods (e.g., HPLC, uPLC, LC-MS, NMR), to determine whether phosphorylation may contribute to the aberrant protein folding and aggregation processes seen in many neurodegenerative diseases. As such, this research will help to address the growing challenge of neurodegenerative diseases in the world by furthering the understanding of disease progression and potentially identifying novel targets/avenues for future treatments.
Student requirements for this project
Minimum of 2.1 in Honours BSc (or equivalent) in Chemistry, Chemical Science, Medicinal Chemistry or Pharmaceutical Science.
Student Stipend € 18,500 p.a.
Materials/ Travel etc € 2,600 p.a.
Applicants for this project are required to complete an Expression of Interest (www.dit.ie/media/documents/study/postgraduateresearch/EOI%20Form.doc) and email it to [email protected]
Deadline to submit applications: Friday 1st October 2021