(UoM - A* STAR) Engineering modular human artificial chromosomes

Rapid advances in DNA synthesis techniques have made it possible to chemically synthesize and modify viruses, biochemical pathways, and bacterial genomes. Over the last decade, our team has led an international consortium to synthesize the world’s first designer eukaryotic genome, the synthetic yeast Sc2.0 project (www.syntheticyeast.org). Genome synthesis not only grants researchers unprecedented control over organisms but also opens up a novel avenue for deepening our understanding of genome biology.

We are now starting to re-imagine the possibilities to reorganise the human genome through extensive genome engineering and re-factoring. Our first step is to engineer modular human neochromosomes to house essential functional gene clusters, which encode essential cellular functionalities such as the chromosome replications, amino acid biosynthesis and metabolism. We have substantial track records in these areas in yeast, for instance, the synthesis of synthetic yeast chromosome II (770Kb, Shen et al., Science 2017) and VII (1M bp, Shen et al., Cell Genomics 2023), relocating all yeast tRNA genes onto a neochromosome (Schindler et al., Cell 2023), engineering yeast rDNAs (Zhang et al., Science 2017) and clustering essential yeast genes in chromosome XII (Luo et al., Genome Biology 2021). In this project, we will first aim to identify a suitable functional gene cluster to work on, and use our technology platform to re-design and synthesise the gene cluster, and re-located it onto a human artificial chromosome (HAC). The HAC(s) will then be transplanted into the recipient cell line and further engineered. In parallel, the endogenous genes in the native human genome will be removed by multiplex genome editing technology. Finally, we will perform trans-omics to phenotype the engineered cell lines.

This engineering biology approach will allow us to probe genome fundamentals which are difficult to explore before, such as genome organisation, minimal sets of genes to reconstitute cellular functions and maintain cell viability, and co-regulation and optimisation of functional clusters.

Expected Start  

October 2025 

Before you Apply  

We recommend that you contact the supervisor(s) for this project on Yizhi.cai@manchester.ac.uk and chewwl@gis.a-star.edu.sg

How to apply 

To be considered for this project, you will need to complete an application here. Please read this page carefully before starting your application.   

When you apply you will be asked to upload the following supporting documents:  

• Personal Statement  
• Final Transcript and certificates of all awarded university level qualifications  
• Interim Transcript of any university level qualifications in progress  
• CV  
• English Language certificate  
• 2 details of academic referees  

In your application, include the project title (UoM - A* STAR)Engineering modular human artificial chromosomes, supervisor Prof Patrick Cai, and funding source Split Site ASTAR and University of Manchester. Select the PhD Chemistry in the programme detail section.  

Applications missing required documents won’t be considered. If documents are unavailable or for further application question please email, email FSE.doctoralacademy.admissions@manchester.ac.uk. 

Eligibility  

1. Hold (or expect to achieve) a First Class or 2:1 UK honours degree (or international equivalent to be checked with The University of Manchester admission team). 

2. Ideally hold a master’s-level qualification at merit or distinction (or international equivalent to be checked with The University of Manchester admission team). 

3. Demonstrable excellent communication skills, including in English language, a proficiency in which should be demonstrably indicated by meeting the requirements as indicated on the University's English language requirements page and in particular securing a minimum IELTS 6.5 overall with a minimum of 6.0 in writing and listening, and 5.5 in all other sub-tests OR securing a TOEFL iBT score of at least 90 with no sub-tests below 20 OR equivalent. Project supervisor teams may recommend a candidate who has excellent English language skills but otherwise has not formal certification of such. Please note that a timely demonstrable minimum English language level is a requirement of the UK Home Office for the issue of student visas to the UK. For some projects an ATAS certificate may also be required by them. 

4. Demonstrate willingness to travel to two partner institutions to complete the programme. 

5. Demonstrate to reflect the Faculty of Science and Engineering Postgraduate Researcher person specification. 

* Educational background matches research project. 

* Potential to form effective working relationships with a diverse range of people, including working inclusively and as part of a team. 

* Potential to take the initiative, lead on projects, and be proactive in prioritising a dynamic, agile and diverse workload. 

* Potential to develop understanding of complex problems, evaluate the strengths and weaknesses of a given scenario, and apply in-depth knowledge to address them. 

* Potential to develop expertise in new areas of the subject. 

* Evidence of an understanding of the proposed area of research, including knowledge of current challenges and opportunities. 

* An interest in continuous personal and professional development. 

* Potential to communicate ideas and conclusions, verbally and in writing, clearly and effectively to specialist and non-specialist audiences. 

* Preliminary knowledge of research techniques/track record of engaging with research. 

* Commitment to principles of Equality, Diversity, Inclusion, and Accessibility in teaching, research, or experience. 

Equality, diversity and inclusion are fundamental to The University of Manchester’s success. Diversity strengthens our research community, enhancing creativity, productivity, quality, and impact. We encourage applicants from diverse backgrounds, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation, or transgender status. 

We also welcome those returning from a career break. Flexible study arrangements (part-time: 50%, 60%, or 80%, depending on the project/funder) may be considered. 

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