Phd Studentship-analytical and Biological Sciences

2 weeks ago

South Mimms, United Kingdom Medicines and Healthcare Products Regulatory Agency Full time

**Details**:
**Reference number**:

- 278737**Salary**:

- £19,800- Funding: Tuition fees for home students as set out by the university are covered; there is provision for laboratory consumables and travel to conferences and the University; there is a student stipend of £ 19,800 p.a.**Job grade**:

- Other**Contract type**:

- Fixed Term**Length of employment**:

- 3 years**Business area**:

- Analytical and Biological Sciences Team within the Science, Research and Innovation operational group (SR&I)**Type of role**:

- Science**Working pattern**:

- Full-time**Number of jobs available**:

- 1Contents

Location

About the job

Things you need to know

Location
- South Mimms, HertfordshireAbout the job

**Job summary**:
**PhD studentship (**PhD_ABS_NIBSC**)**

A 3-year full-time PhD studentship is available in the Analytical and Biological Sciencies Team within the Science, Research and Innovation operational group (SR&I) of the Medicines and Healthcare Products Regulatory Agency (MHRA), in collaboration with the department of Biochemical Engineering at University College London. The project will be supervised by Drs Tim Rudd, Paul Matejtschuk and Gail Whiting at MHRA and Professor Paul Dalby at UCL. The studentship is anticipated to commence on October 1st 2023.

**About the Project**

**Mapping functionally important regions in biotherapeutic proteins through combined use of high-end analytical techniques and molecular modelling.**

A molecular understanding of the basis of biological function is a key area for research, both in the delivery of biotherapeutics and in the preparation of suitable reference materials and powerful activity indicating biological assays. Recent advances in the use of high-end molecular characterisation, Hydrogen deuterium exchange mass spectrometry (HDX-MS) and heteronuclear isotope-labelled nuclear magnetic resonance (NMR) spectroscopy, have allowed greater understanding of the interaction between protein molecules, their stability, interaction with target molecules and control of function. Complementary to experiment, the increased use of molecular dynamics (MD), facilitated by high performance computing, have also contributed useful insight into these areas.

The hypothesis for the PhD project is that MD coupled with high-end NMR spectroscopy and mass spectrometry (MS) can help us to elucidate the molecular basis of differences in biological activity in glycosylated and non-glycosylated biomolecules and help bio-design more effective biological medicines. An ideal model system to start the investigation is G-CSF, which has pharmaceutical variants which are non-glycosylated, glycosylated and pegylated.

Furthermore, once the glycosylated protein system is understood the effect of formulation excipients can be investigated. The basis of the project is to combine 1H-15N HSQC NMR experiments measured over a temperature gradient, with detailed MD studies, allowing amino acids/regions of the protein that are less stable to be identified, providing in depth structural information. Direct comparison of non-glycosylated/glycosylated forms of the protein of interest will allow the effect of glycosylation on the structure, dynamics and stability of the protein to be identified and this can be correlated with biological properties.

In addition, MS will be used to identify atomistic information, pertaining to structural degradation and the effects glycosylation have on the molecules, for example glyco-peptide analysis and the identification of solvent accessible amino acids. Comparing the glycosylated and non-glycosylated forms, and also different formulations, will relate their impact on structural dynamics to the stability of the protein itself, enabling improved formulation as an ideal protein drug product.

**Job description**:
**About MHRA**

The Medicines and Healthcare products Regulatory Agency enhances and improves the health of millions of people every day through the effective regulation of medicines and medical devices, underpinned by science and research.

**About SR&I**

**About the Team**

The Formulation Science and Laboratory of Molecular Analysis teams, within the Analytical and Biological Sciences Division of SR&I, are leaders in the formulation and analysis of biological medicines, studying their structure, stability and other physicochemical properties. This underpins the development of many WHO international standards and supports of the R&D and Control Testing functions of the MHRA.

**Awarding Institution**

**Person specification**:
**About You**

Your key responsibilities will be:

- To undertake the research projects in line with the project aims.
- To communicate effectively, orally and through written media, undertake presentations at scientific meetings and maintain excellent records.
- To interact regularly and effectively with your supervisors and interact appropriately and effectively with other staff.
- To meet the expectations of the study for a PhD

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