DNA-bending Proteins for Nanotech

DNA is the molecule that nature uses as genetic material and it rarely exists in a relaxed state inside cells. Rather, DNA is subjected to mechanical deformations like torsion, bend or stretch, which are induced by proteins and which facilitate the realization of all the different genetic transactions such as recombination, gene expression and replication. In particular, the formation of closed DNA loops is directly associated with the regulation of genes.

Nucleoid-associated proteins (NAPs) are a collection of DNA-interacting proteins that perform crucial roles of organization, packaging, and gene regulation in prokaryotic chromosomes. Integration host factor (IHF) is a key NAP in Escherichia coli and other Gram-negative bacteria. Its architectural role is thought to involve creating some of the sharpest bends observed in DNA.

The relevance of DNA not only comes from biology but also lately has been applied in the field of nanotechnology. The remarkable specificity of the interactions between complementary bases makes DNA a construction material that can be used in the design of nano-architectures or artificial molecular machines such as DNA tweezers or DNA walkers. However, DNA has other degrees of freedom, apart from the ones related with the specific base-pairing rules, that have not been exploited for engineering, including, for example, torsion and bending.

The aim of this project is to exploit the DNA bending induced by IHF for designing unique and exclusive DNA topologies. We plan to study which is the DNA bending angle that IHF imposes depending on different binding sites. We then plan to choose the one that causes a more bistable mechanical switch on the DNA so we can program the formation of closed DNA loops.

In our previous study (Yoshua & Watson, NAR, 2021), we compared atomic force microscopy (AFM) with all-atom molecular dynamics simulations (MDS) for the same DNA-IHF complexes. You will apply and extend the same methodology to new DNA sequences. Because you will learn both experimental and computational skills in biophysics, microbiology, and computational chemistry, you will have a unique set of skills that are in high demand in the biotechnology field.

The success of this project would enable us to design DNA constructs for testing different biological hypothesis related with the role of DNA architecture in genomic function and would give a total new dimensionality to DNA technology.

Informal enquiries should be made to either Dr Agnes Noy (agnes.noy@york.ac.uk).

How to apply:

Applicants should apply via the University’s online application system . Please read the application guidance first so that you understand the various steps in the application process.

Funding:

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.