PhD (October 2024 start)

at  National Institute for Bioprocessing Research and Training NIBRT

VACANCY SUMMARY

This is an exciting, 4-year PhD opportunity for an exceptional candidate to work on, and influence, a research programme funded through a prestigious SFI Research Professorship award to Professor Mark Smales in the area of enhancing advanced biotherapeutic biological medicines design, manufacturing and activity at NIBRT. There is a growing portfolio of advanced biotherapies, including modalities such as gene therapies, cell therapies and RNA therapeutics as vaccines and therapeutics, for which the manufacturing processes are often low yielding and inefficient. The role will help deliver a work programme to generate a fundamental, transformative and conceptual mechanistic shift in our understanding of the cell expression systems and processes used to produce these advanced biotherapeutics, and apply modern engineering biology approaches to deliver more efficient, predictable, and affordable manufacturing approaches. The PhD candidate will be expected to (1) undertake the work and training programme outlined in the grant proposal ‘Enhancing Advanced Biotherapeutic Design, Manufacturing and Activity: Defining and Leveraging the Biological Rules that Underpin AAV Gene Therapy, IVTmRNA and Protein Biotherapeutic Modality Design and Production’ for PhD1, and (2) provide technical and laboratory support for other members of Prof Smales team at NIBRT.

ROLE PURPOSE

The main focus of the project will be to work on the development of a better understanding of the biology of HEK293 cells and genetic components of the target genome that underpin rAAV vector production and apply this to generate new HEK293 hosts, bioprocesses and vectors for improved manufacturing. Specific objectives are to deliver: (1) a fundamental understanding of the impact of rAAV production on the HEK293 cell factory and its ability to produce rAAV at high yield and quality; (2) determine the cellular constraints in HEK293 cells and systems that limit production of functional (fully packaged) rAAV vectors; (3) utilise cell engineering and synthetic biology approaches to generate new HEK293 cell hosts that aid intensification of cell bioprocesses to enhance yield of rAAV, and (4) manipulate genome genetic elements to tune their expression in a tissue specific manner. These outcomes have the potential to deliver a step-change in our understanding of rAAV production processes alongside application of this knowledge to generate new HEK293 hosts and bioprocesses for improved manufacturing of rAAVs.

KEY RESPONSIBILITIES

The key responsibilities of the job include:

• To undertake appropriate experiments to achieve the goals and milestones as described in the Research Professorship SFI funded grant programme “Enhancing Advanced Biotherapeutic Design, Manufacturing and Activity: Defining and Leveraging the Biological Rules that Underpin AAV Gene Therapy, IVTmRNA and Protein Biotherapeutic Modality Design and Production”, specifically those associated to PhD1 in WP1 around recombinant AAV production from HEK293 cells.
• To undertake the mandatory training, reporting, public engagement/outreach activities and any other requirements outlined under the funding agreement for the project.
• Be responsible for maintenance of laboratory records, health and safety records, and inventory around the project.
• To interact with other collaborators at NIBRT and externally, both within Ireland and internationally, coordinating activity across the consortium including the exchange of reagents.
• Regularly report to the PI and supervisors, compile data acquired in a form to allow rapid transformation of documented research results into high quality research papers and/or patent applications.
• Attend and present at training activities and research summits and meetings as outlined in the wider programme.
• Be committed to your own personal career development, including continually updating knowledge and understanding in fields related to the research area.
• Other duties, commensurate with the grading of the job, as assigned from time to time.