How can DNA condensate despite its negative charge? Implications in genome regulation, antibiotic resistance and gene therapy

About the Project

DNA molecules, being highly negatively charged, naturally repel each other. However, in the presence of multivalent ions or specific proteins, they can overcome this repulsion and condense into compact structures. Remarkably, DNA strands with similar (homologous) sequences tend to aggregate even more strongly — a phenomenon whose molecular basis remains poorly understood.

DNA condensation underpins a wide range of biological processes, including genome organization and homologous recombination. It also contributes to the structural integrity of bacterial biofilms—complex microbial communities that serve as protective barriers against antibiotics. Understanding and disrupting DNA-driven biofilm stability could therefore open new avenues to combat antimicrobial resistance, one of the most urgent health challenges of our time. Moreover, DNA condensation plays a key role in enhancing the efficiency of DNA-based vaccines, as it reduces their molecular volume and facilitates cellular uptake. Finally, it is fundamental to the development of DNA-based hydrogels and nanostructures in the field of DNA nanotechnology.

In this PhD project, you will use computational simulations to uncover the factors that control DNA condensation and sequence-specific aggregation. You will:

• Investigate how multivalent ions and proteins neutralize DNA’s electrostatic repulsion.
• Explore how DNA sequence similarity influences molecular recognition and aggregation.
• Apply in silico drug screening methods to target a bacterial protein–DNA interaction recently identified by Dr. Noy and collaborators, with the aim of disrupting biofilm stability.
• Study the condensation of DNA minicircles used in gene therapy, leveraging recent structural and dynamical insights from the Noy group.

Your work will have wide-ranging implications for antimicrobial resistance, biotechnology, and therapeutic DNA delivery.

Research Environment

This project will be supervised by Dr. Agnes Noy, a pioneer in the computational modelling of DNA aggregation and DNA minicircles [1–4]. You will work at the intersection of several ongoing collaborations within her group, benefiting from a vibrant, interdisciplinary research environment. Collaborators include:

• Prof. Alice Pyne (University of Sheffield)—experimental studies of DNA condensation and DNA vaccines
• Prof. Davide Michieletto (University of Edinburgh)—DNA nanotechnology and biofilms
• Prof. Martin Falscione (Department of Chemistry, University of York)—biofilm structure and stability
• Dr. Daniel Cole (Newcastle University)—computational drug design.

As a PhD student, you will become part of the vibrant and interdisciplinary Physics of Life Group at the University of York. You will also benefit from a wide range of tailored training opportunities, including workshops, summer schools, and scientific seminars, all designed to support your professional and personal development. These activities will take place both at York and through the UK-wide Physics of Life network (www.physicsoflife.org.uk), providing you with valuable opportunities to connect and collaborate with researchers across the country.

Training and Career Development

You will gain:

• Expertise in widely-used molecular modeling software employed across the pharmaceutical, biotech, and chemical industries.
• Strong programming and data analysis skills, opening potential career paths in data science and software engineering.
• Broad interdisciplinary knowledge spanning biology, chemistry, and physics.

This is an exceptional opportunity to contribute to the future of bioengineering and biotechnology while developing a versatile and highly sought-after skill set. You will find more information of Dr. Noy’s research at:

• Website: agnesnoylab.wordpress.com
• X (Twitter): @ANoyLab
• LinkedIn: linkedin.com/in/agnesnoy

Do not hesitate to make informal enquiries to Dr. Agnes Noy (agnes.noy@york.ac.uk)

Entry requirements:

Candidates should have (or expect to obtain) a minimum of a UK upper second class honours degree (2:1) or equivalent in Physics, Chemistry, Biology, Computer Science, Mathematics, or a closely related subject.

How to apply:

Applicants should apply via the University’s online application system at https://www.york.ac.uk/study/postgraduate-research/apply/. Please read the application guidance first so that you understand the various steps in the application process.

This project is open-ended making it suitable for MSc by Research and PhD level . Dr. Noy has experience in publishing articles with master students[5]

Funding Notes

This is a self-funded project and you will need to have sufficient funds in place (eg from scholarships, personal funds and/or other sources) to cover the tuition fees and living expenses for the duration of the research degree programme. Please check the School of Physics, Engineering and Technology website for details about funding opportunities at York.