Unravelling the knotty process of gene expression

News

>>>

Scientists create first billion-atom biomolecular simulation
Modeling genes at the atomistic level is the first step toward creating a complete explanation of how DNA expands and contracts, which controls genetic on/off switching.

>>>

Scientists create first billion-atom biomolecular simulation

Researchers at Los Alamos National Laboratory have created the largest simulation to date of an entire gene of DNA, a feat that required one billion atoms to model and will help researchers to better understand and develop cures for diseases like cancer.

READ MORE

 ­

The Biology of Gender, from DNA to the Brain
How does gender work? It's not just about our chromosomes, says biologist Karissa Sanbonmatsu. In this TEDWomen talk, she shares new discoveries from epigenetics, the emerging study of how DNA activity can permanently change based on social factors like trauma or diet.

 ­

Published Research

Scaling molecular dynamics beyond 100,000 processor cores for large‐scale biophysical simulations

Journal of Computational Chemistry | April 2019
Karissa Sanbonmatsu, et al.
Abstract

The growing interest in the complexity of biological interactions is continuously driving the need to increase system size in biophysical simulations, requiring not only powerful and advanced hardware but adaptable software that can accommodate a large number of atoms interacting through complex forcefields. To address this, we developed and implemented strategies in the GENESIS molecular dynamics package designed for large numbers of processors. Long‐range electrostatic interactions were parallelized by minimizing the number of processes involved in communication. A novel algorithm was implemented for nonbonded interactions to increase single instruction multiple data (SIMD) performance, reducing memory usage for ultra large systems. Memory usage for neighbor searches in real‐space nonbonded interactions was reduced by approximately 80%, leading to significant speedup. Using experimental data describing physical 3D chromatin interactions, we constructed the first atomistic model of an entire gene locus (GATA4). Taken together, these developments enabled the first billion‐atom simulation of an intact biomolecular complex, achieving scaling to 65,000 processes (130,000 processor cores) with 1 ns/day performance.

READ MORE

 ­

Mesoscale Modeling Reveals Hierarchical Looping of Chromatin Fibers Near Gene Regulatory Elements

The Journal of Physical Chemistry | May 2016
Karissa Sanbonmatsu, et al.
Abstract

While it is well-recognized that chromatin loops play an important role in gene regulation, structural details regarding higher order chromatin loops are only emerging. Here we present a systematic study of restrained chromatin loops ranging from 25 to 427 nucleosomes (fibers of 5–80 Kb DNA in length), mimicking gene elements studied by 3C contact data. We find that hierarchical looping represents a stable configuration that can effectively bring distant regions of the GATA-4 gene together, satisfying connections reported by 3C experiments. Additionally, we find that restrained chromatin fibers larger than 100 nucleosomes (∼20Kb) form closed plectonemes, whereas fibers shorter than 100 nucleosomes form simple hairpin loops. By studying the dependence of loop structures on internal parameters, we show that loop features are sensitive to linker histone concentration, loop length, divalent ions, and DNA linker length.

READ MORE

 ­

Tunable Riboregulator Switches for Post-transcriptional Control of Gene Expression

ACS Synthetic Biology | Decmember 2015
KY Sanbonmatsu, et al.
Abstract

Until recently, engineering strategies for altering gene expression have focused on transcription control using strong inducible promoters or one of several methods to knock down wasteful genes. Recently, synthetic riboregulators have been developed for translational regulation of gene expression. Here, we report a new modular synthetic riboregulator class that has the potential to finely tune protein expression and independently control the concentration of each enzyme in an engineered metabolic pathway. This development is important because the most straightforward approach to altering the flux through a particular metabolic step is to increase or decrease the concentration of the enzyme.

READ MORE

 ­

Videos

 

How You Know You're in Love: Epigenetics, Stress & Gender Identity
Social interactions alter DNA (epigenetics). Revealing how her own gender transition led her down the path of epigenetics, Scientist Karissa Sanbonmatsu takes us on a journey to DNA rave parties and the science of love.

 

Photos

    Black download iconA Los Alamos-led team created the largest simulation to date of an entire gene of DNA, a feat that required one billion atoms to model.

    Black download iconResearchers used the Los Alamos supercomputer Trinity to create the first billion-atom biomolecular simulation.


    Expert

     
    Karissa Sanbonmatsu | Los Alamos National Laboratory

    Karissa Sanbonmatsu

    With her team, Sanbonmatsu uses computational and experimental approaches to understand the mechanism of a diverse array of non-coding RNA systems.

     

    Contact

    Charles Poling, (505) 257-8006, cpoling@lanl.gov
    Nick Njegomir, (505) 665-9394, 
    nickn@lanl.gov

    Newsroom