Biomedical subjects

Erez Braun

Publications and source records attributed to Erez Braun.

5 recordsLinked to original sources

PubMed2006

Dynamics of protein distributions in cell populations.

A population of cells exhibits wide phenotypic variation even if it is genetically homogeneous. In particular, individual cells differ from one another in the amount of protein they express under a given regulatory system under fixed conditions. Here we study how protein distributions in a population of the yeast S. cerevisiae are shaped by a balance of processes: protein production--an intracellular process--and protein dilution due to cell division--a population process. We measure protein distributions by employing reporter green fluorescence protein (gfp) under the regulation of the yeast GAL system under conditions where it is metabolically essential. Cell populations are grown in chemostats, thus allowing control of the environment and stable measurements of distribution dynamics over many generations. Despite the essential functional role of the GAL system in a pure galactose medium, steady-state distributions are found to be universally broad, with exponential tails and a large standard-deviation-to-mean ratio. Under several different perturbations the dynamics of the distribution is observed to be asymmetric, with a much longer time to build a wide expression distribution from below compared with a fast relaxation of the distribution toward steady state from above. These results show that the main features of the protein distributions are largely determined by population effects and are less sensitive to the intracellular biochemical noise.

Actins↗

PubMed2006

Synthetic gene recruitment reveals adaptive reprogramming of gene regulation in yeast.

The recruitment of a gene to a foreign regulatory system is a major evolutionary event that can lead to novel phenotypes. However, the evolvability potential of cells depends on their ability to cope with challenges presented by gene recruitment. To study this ability, we combined synthetic gene recruitment with continuous culture and online measurements of the metabolic and regulatory dynamics over long timescales. The gene HIS3 from the histidine synthesis pathway was recruited to the GAL system, responsible for galactose utilization in the yeast S. cerevisiae. Following a switch from galactose to glucose--from induced to repressed conditions of the GAL system--in histidine-lacking chemostats (where the recruited HIS3 is essential), the regulatory system reprogrammed to adaptively tune HIS3 expression, allowing the cells to grow competitively in pure glucose. The adapted state was maintained for hundreds of generations in various environments. The timescales involved and the reproducibility of separate experiments render spontaneous mutations an unlikely underlying mechanism. Essentially all cells could adapt, excluding selection over a genetically variable population. The results reveal heritable adaptation induced by the exposure to glucose. They demonstrate that genetic regulatory networks have the potential to support highly demanding events of gene recruitment.

Adaptation, Biological↗

PubMed2004

Transient responses and adaptation to steady state in a eukaryotic gene regulation system.

Understanding the structure and functionality of eukaryotic gene regulation systems is of fundamental importance in many areas of biology. While most recent studies focus on static or short-term properties, measuring the long-term dynamics of these networks under controlled conditions is necessary for their complete characterization. We demonstrate adaptive dynamics in a well-known system of metabolic regulation, the GAL system in the yeast S. cerevisiae. This is a classic model for a eukaryotic genetic switch, induced by galactose and repressed by glucose. We followed the expression of a reporter gfp under a GAL promoter at single-cell resolution in large population of yeast cells. Experiments were conducted for long time scales, several generations, while controlling the environment in continuous culture. This combination enabled us, for the first time, to distinguish between transient responses and steady state. We find that both galactose induction and glucose repression are only transient responses. Over several generations, the system converges to a single robust steady state, independent of external conditions. Thus, at steady state the GAL network loses its hallmark functionality as a sensitive carbon source rheostat. This result suggests that, while short-term dynamics are determined by specific modular responses, over long time scales inter-modular interactions take over and shape a robust steady state response of the regulatory system.

Biophysical Phenomena↗

PubMed2003

DNA-templated carbon nanotube field-effect transistor.

The combination of their electronic properties and dimensions makes carbon nanotubes ideal building blocks for molecular electronics. However, the advancement of carbon nanotube-based electronics requires assembly strategies that allow their precise localization and interconnection. Using a scheme based on recognition between molecular building blocks, we report the realization of a self-assembled carbon nanotube field-effect transistor operating at room temperature. A DNA scaffold molecule provides the address for precise localization of a semiconducting single-wall carbon nanotube as well as the template for the extended metallic wires contacting it.

Bacteriophage lambda↗

PubMed2002

Sequence-specific molecular lithography on single DNA molecules.

Recent advances in the realization of individual molecular-scale electronic devices emphasize the need for novel tools and concepts capable of assembling such devices into large-scale functional circuits. We demonstrated sequence-specific molecular lithography on substrate DNA molecules by harnessing homologous recombination by RecA protein. In a sequence-specific manner, we patterned the coating of DNA with metal, localized labeled molecular objects and grew metal islands on specific sites along the DNA substrate, and generated molecularly accurate stable DNA junctions for patterning the DNA substrate connectivity. In our molecular lithography, the information encoded in the DNA molecules replaces the masks used in conventional microelectronics, and the RecA protein serves as the resist. The molecular lithography works with high resolution over a broad range of length scales from nanometers to many micrometers.

Antibodies↗