The mechanical genome : inquiries into the mechanical function of genetic information

The four possible segments A, T, C and G that link together to form DNA molecules, and with their ordering encode genetic information, are not only different in name, but also in their physical and chemical properties. The result is that DNA molecules with different sequences have different physical behavior. For instance, one sequence may lead to a very flexible DNA molecule, another to a very stiff one. A DNA molecule with a given sequence may be straight, or intrinsically curved. This leads to an interplay between the information stored in a DNA molecule on one hand, and the physical properties of that molecule on the other. This is of great importance in our cells, where lengths of DNA far longer than the size of the cells that contain them need to be significantly folded up. The research presented in this thesis looks at how we can model this interplay, what its effects can be, and whether nature has made use of it to encode mechanical signals into real genomes.Theoretical Physic

Performing SELEX experiments in silico

Theoretical Physic

Genomes of multicellular organisms have evolved to attract nucleosomes to promotor regions

Theoretical Physic

Constraining the neutron star equation of state with gravitational wave signals from coalescing binary neutron stars

Recently exploratory studies were performed on the possibility of constraining the neutron star equation of state (EOS) using signals from coalescing binary neutron stars, or neutron star–black hole systems, as they will be seen in upcoming advanced gravitational wave detectors such as Advanced LIGO and Advanced Virgo. In particular, it was estimated to what extent the combined information from multiple detections would enable one to distinguish between different equations of state through hypothesis ranking or parameter estimation. Under the assumption of zero neutron star spins both in signals and in template waveforms and considering tidal effects to 1 post-Newtonian (1PN) order, it was found that O(20) sources would suffice to distinguish between a stiff, moderate, and soft equation of state. Here we revisit these results, this time including neutron star tidal effects to the highest order currently known, termination of gravitational waveforms at the contact frequency, neutron star spins, and the resulting quadrupole-monopole interaction. We also take the masses of neutron stars in simulated sources to be distributed according to a relatively strongly peaked Gaussian, as hinted at by observations, but without assuming that the data analyst will necessarily have accurate knowledge of this distribution for use as a mass prior. We find that especially the effect of the latter is dramatic, necessitating many more detections to distinguish between different EOSs and causing systematic biases in parameter estimation, on top of biases due to imperfect understanding of the signal model pointed out in earlier work. This would get mitigated if reliable prior information about the mass distribution could be folded into the analyses

Multiplexing genetic and nucleosome positioning codes: A computational approach

Theoretical PhysicsBiological and Soft Matter Physic

Force responses of strongly intrinsically curved DNA helices deviate from worm-like chain predictions

DNA sequences with nontrivial intrinsic curvature are of interest for a range of biological and artificial DNA systems. We design both intrinsically strongly curved and intrinsically straight sequences. We find that such sequences with opposing curvatures can be designed even under constraints that would naively lead one to assume that those sequences would be highly similar in their mechanical properties. We then characterize the force response of those sequences and find that their force-extension curves deviate significantly in the low-force regime, and that the standard worm-like chain description is inadequate to describe the low-force response of the strongly bent sequences. We propose a modified description that takes the intrinsic curvature into account, making the DNA act, in the low-force regime, like a nanoscale helical spring. We find strongly improved agreement between the model and the simulated force-extension curves

Can Markov chain models predict nucleosome positioning?

Theoretical Physic

Force responses of strongly intrinsically curved DNA helices deviate from worm-like chain predictions

DNA sequences with nontrivial intrinsic curvature are of interest for a range of biological and artificial DNA systems. We design both intrinsically strongly curved and intrinsically straight sequences. We find that such sequences with opposing curvatures can be designed even under constraints that would naively lead one to assume that those sequences would be highly similar in their mechanical properties. We then characterize the force response of those sequences and find that their force-extension curves deviate significantly in the low-force regime, and that the standard worm-like chain description is inadequate to describe the low-force response of the strongly bent sequences. We propose a modified description that takes the intrinsic curvature into account, making the DNA act, in the low-force regime, like a nanoscale helical spring. We find strongly improved agreement between the model and the simulated force-extension curves

Can Markov Chain Models Predict Nucleosome Positioning

Theoretical Physic