Description:

We are a team headed by Dr Matias I Autio, Senior Scientist in the Laboratory of Systems Biology & Data Analytics.

We are embarking on an STDR funded proof-of-concept project to establish a method for generating genome-engineered induced pluripotent stem cells for use in cell therapy. The project is closely linked with industrial partners and the aim is to translate the results eventually into the clinic.

We are looking for a Post Doctoral Fellow to drive the research activities for the duration of the project.

Project Summary:

The next generation of cell therapies will utilize targeted integration of therapeutic payload transgenes into the genome of the cells. For disease indications where the engineered therapeutic cells require large or multiple payload transgenes, successful transgene integration poses drastic challenges. These challenges include, for example efficiency, random integration of transgenes and off-target effects. To address the above challenges, we have identified a shortlist of human genomic safe harbours (GSH), safe sites for transgene integration in the genome, and validated a selection of them in pluripotent stem cells and their differentiated progeny. We have also built a suite of non-viral tools for precise targeting of our GSH which offer un-paralleled transgene integration efficiency in human pluripotent stem cells (PSC). Together, the validated GSH and a toolbox for their targeted transgene integration offer a platform for engineering human induced PSC (hiPSCs) with large modular therapeutic payloads for multiple different disease indications. One application for our technology would be the generation of a series of hypoimmunogenic hiPSC lines that can be used as the basis for allogeneic cell therapy. Upon knockout of HLA genes, the edited hiPSCs can be further modified by integrating immune modulatory genes at the validated GSH sites to improve immune tolerance against different allogeneic immune attack pathways. Subsequently, hiPSCs can be differentiated into pancreatic islet cells and transplanted in Type 1 diabetes (T1D) patients to restore endogenous insulin production potentially without the need for routine immunosuppressants. This strategy is essential for overcoming the immunogenicity of transplanted cells and providing greater safety and accessibility to patients in need.

This project is run in close collaboration with A/Prod Adrian Teo?s team from IMCB, as well as our industrial collaborator BetaLife Pte Ltd.

Responsibilities:

• Lead the hands-on experiments and operations to engineer human cells.
• Follow analytical procedures and instrumental operation guidelines.
• Perform data collection and manage research data and notes.
• Assist the team with the maintenance of smooth and safe operation in the working environment.
• Ensure project deliverables are met in a timely manner and to the highest standard

Requirements:

• Expert knowledge of laboratory-based methodologies such as nucleic acid extraction, molecular cloning, human pluripotent stem cell culture & differentiation
• Extensive experience with human pluripotent stem cell culture and genome editing is preferred.
• Good organizational skills and ability to multitask.
• Highly motivated, keen to learn and committed to laboratory work.
• Able to work independently and as part of a team.
• Good communication (verbal and written) and presentation skills.
• Experience with computational work flows is preferred

The above eligibility criteria are not exhaustive. A*STAR may include additional selection criteria based on its prevailing recruitment policies. These policies may be amended from time to time without notice. We regret that only shortlisted candidates will be notified.