arXiv subjects

Reiner Siebert

Publications and source records attributed to Reiner Siebert.

2 recordsLinked to original sources

arXiv2024

Effect of environmental noise on charge diffusion in DNA: Towards modeling its potential epigenetic impact in live processes

Charge diffusion through desoxyribonucleic acid (DNA) is a physico-chemical phenomenon that on the one hand is being explored for technological purposes, on the other hand is applied by nature for various informational processes in life. With regard to the latter, increasing experimental and theoretical evidence indicates that charge diffusion through DNA is involved in basic steps of DNA replication and repair, as well as regulation of gene expression via epigenetic mechanisms such as DNA methylation or DNA binding of proteins. From the physics point of view, DNA supports a metallic-like behavior with long-range charge mobility. Nevertheless, particularly considering a living environment, charge mobility in DNA needs to take into account omnipresent noise and disorder. Here, we analyze quantum diffusion of single charges along DNA-inspired two-dimensional tight-binding lattices in presence of different sources of intrinsic and environmental fluctuations. It is shown that double-strand lattices, parametrized according to atomistic calculations of DNA sequences, offer a complex network of pathways between sites and may give rise to long-distance coherence phenomena. These effects strongly depend on carrier type (electrons, holes), the energetic profile of the lattice (composition) as well as the type of noise and disorder. Of particular interest are spatially correlated low-frequency fluctuations which may support coherent charge transfer over distances of a few sites. Our results may trigger further experimental activities aiming at investigating charge mobility in DNA both in the native in-vivo context as well as on artificial platforms.

physics.bio-ph↗

arXiv2015

Cancer initiation with epistatic interactions between driver and passenger mutations

We investigate the dynamics of cancer initiation in a mathematical model with one driver mutation and several passenger mutations. Our analysis is based on a multi type branching process: We model individual cells which can either divide or undergo apoptosis. In case of a cell division, the two daughter cells can mutate, which potentially confers a change in fitness to the cell. In contrast to previous models, the change in fitness induced by the driver mutation depends on the genetic context of the cell, in our case on the number of passenger mutations. The passenger mutations themselves have no or only a very small impact on the cell's fitness. While our model is not designed as a specific model for a particular cancer, the underlying idea is motivated by clinical and experimental observations in Burkitt Lymphoma. In this tumor, the hallmark mutation leads to deregulation of the MYC oncogene which increases the rate of apoptosis, but also the proliferation rate of cells. This increase in the rate of apoptosis hence needs to be overcome by mutations affecting apoptotic pathways, naturally leading to an epistatic fitness landscape. This model shows a very interesting dynamical behavior which is distinct from the dynamics of cancer initiation in the absence of epistasis. Since the driver mutation is deleterious to a cell with only a few passenger mutations, there is a period of stasis in the number of cells until a clone of cells with enough passenger mutations emerges. Only when the driver mutation occurs in one of those cells, the cell population starts to grow rapidly.

q-bio.PE↗