The Materials Theme in the SSPC Science Foundation Ireland Research Centre for Pharmaceuticals (www.sspc.ie) is looking for a Chemistry, Biochemistry or Biochemical/Chemical Engineering graduate interested in a PhD in the area of peptide crystallisation.
Host Institute: University of Limerick (Dept. of Chemical Sciences and Bernal Institute)
Start Date: August 2021
Scholarship: €18,000 stipend per annum and PhD fees covered for 4 years.
Supervisors: Prof. Tewfik Soulimane and Dr Sarah Hudson.
How to Apply: Please send a cover letter, a CV and a transcript of your BSc and/or MSc degrees to [email protected] before 31st March 2021.
Project Title: Exploration of peptide crystallization processes for the purpose of improved predictability and control of product properties for pharmaceutical applications.
Brief Project Description: This PhD project will explore the fundamentals of bulk peptide crystallisation and its’ potential as an approach for the purification and processing of solid state peptide therapeutics. It will explore the possibility of using crystallisation to improve the solid state properties of peptides with a focus on antimicrobial peptides. This project will sit within the SSPC’s advanced Materials research programme, in the crystallisation section. The PhD will involve the solution and solid state characterisation and solubility determination of a selected model peptide in a range of aqueous and organic media. An array of experimental conditions will be screened for the generation of seed crystals and single crystal structure determination. From this screening, conditions that are scalable and generate peptide crystals will be identified. Further crystallisation parameters (e.g. temperature, peptide concentration, pH, precipitants, seeding, etc) will be varied to obtain peptide crystals at larger scale with control over particle size and degree of crystallinity. X-ray diffraction and HPLC analysis will be used to determine crystallinity and purity respectively. It is known that there is a narrow window of experimental conditions that will generate peptide crystals, thus, a panel of model peptides will be assessed with the most successful candidate moving forward to scaled up crystallisation studies. The scaled up crystallisation experiments will be conducted in chemical synthesis reactors (Easymax, Optimax from Mettler Toledo) with controlled temperature and overhead stirring with a range of process analytical technologies (PAT) including FTIR, Raman, PVM, FBRM in situ probes to generate inline measurements of the nucleation and crystal growth processes. Crystallisation will be induced within the reactors using anti-solvent addition, pH variation, seed crystal addition or temperature variation. The impact of stirring, changing rates of addition, number of seed crystals etc. will be monitored for the impact on the properties of the crystallised product.
