DNA topology
Just like in any long polymer, DNA tends to form knots. These are detrimental of cell function and therefore, understanding how proteins simplify the topology of DNA molecules is one of the most intriguing open questions in genome and biophysics. In this project we ask if there exist some local geometric properties of 3D curves that capture their “knottedness” (spoiler, there are). We also compare different mechanisms to find the most efficient way in which type2-topoisomerase (TopoII), an enzyme that ”cuts” and ”reseals” double-stranded DNA, finds and resolves DNA knots.
- Sleiman et al, ACS polymers Au 2022
- Michieletto et al, NAR 2022
Self assembling materials
In this project DNA is programmed to hierarchically self-assemble into superstructures (DNA hydrogels and nanosheets) spanning from nano to micrometer scales. Using experiments and simulations we study the fundamental aspects of how to relate the macroscopic viscoelastic properties of these materials to the underlying molecular structure of the DNA building-blocks. Furthermore, our designs encode sequences for the action of proteins that can digest the system and therefore change its mechanical properties.
- Keitel Salguero, et al, Molecules 2023
- Giogia Palombo, et al, “Topological nature of elasticity in networks with limited valence”, in preparation.
- Giogia Palombo, et al, “Programmable degradation of DNA hydrogels”, in preparation.
DNA elasticity
Since the discovery of the structure of DNA, the geometry of the double-helix and its topological implications have engaged and fascinated the scientific community. It is becoming more and more evident that not only is the genetic information encoded in the DNA sequence of primary importance, but also that changes in its three-dimensional structure can alter crucial biological functions, such as gene expression and replication. On top of this, DNA interacts with a variety of proteins, which causes its deformation (bending, twisting, stretching). Therefore, understanding the mechanical properties of DNA is essential to understand its function. In this project we use Molecular Dynamics simulations to shed some light onto this subject.
- Fosado et al, PRL 2023
- Fosado et al, Soft Matter 2020
- Fosado et al, Soft Matter 2016
The role of supercoiling in the Biophysics of DNA
The discovery of the helical structure of DNA in 1953 revealed the mechanism by which genetic information – with the instructions to accomplish the biological function of all living organisms – is stored. However, its peculiar helical shape would also raise several questions about the organization of DNA inside a cell and its functioning. The problem is easily seen if we think about an old fashioned telephone cord, which has been assembled with a spiral shape similar to that of DNA. Any attempt to over or under twist the cord will cause it to writhe up, a phenomenon known as supercoiling. In the case of DNA, the regulation of supercoiling is important because it permits (or prevents) access to the information encoded along its backbone. To complicate the picture even more, supercoiling takes place in the intracellular environment where DNA interacts with other elements, such as proteins, that continuously change its shape. In this project we use Molecular Dynamics simulations to study (i) the effect of supercoiling on DNA melting; (ii) the dynamics of supercoiling under physiological conditions during transcription; and (iii) the relation between supercoiling and DNA-binding proteins.
- Fosado et al, PNAS 2021.
- Fosado el al, PRL 2017.
