Alistair Boettiger
Stanford University, CA·Biophysics
Inside every cell nucleus, DNA is folded in three dimensions, and that folding helps decide which genes turn on. Enhancers, DNA switches that boost gene activity, must physically come close to the promoters, the start sites of genes, that they control.
- Fields
Biophysics
Genetics
Biology
- Topics
3D genome
chromatin organization
gene regulation
- Grants
- 1 known grant, through Jul 2029
What they work on
- Measure how genomic distance and context shape 3D-genome motion, meaning the frequency, speed and timescales of contacts, at a simple and a complex locus using TRACK-IT live imaging with transposon-tiled fluorescent DNA labels.
- Test which molecular processes drive 3D-genome motion, including cohesin loop extrusion, transcription and topoisomerase activity, using genetic and pharmacological perturbations during high-speed live imaging.
- Build biophysical simulations of high-time-resolution genome motion to predict how candidate mechanisms could speed enhancer-promoter communication and to interpret live-microscopy data.
- Track the 3D motion of estrogen-inducible enhancers and their promoters around transcription bursts with TRACK-EP, comparing active and inactive elements from a synchronized time zero.
More about the research
Snapshots from single-cell methods, including Optical Reconstruction of Chromatin Architecture (ORCA) developed in this lab, together with theoretical models, suggest the 3D genome is flexible and constantly moving. Watching that motion in living cells has been limited by poor resolution in space and time and by the difficulty of adding fluorescent labels to DNA.
Why it matters
Genes and their regulatory switches constantly connect and separate as they direct cell behavior, and the genome's 3D organization shapes development and health and disease states. Tools to watch this motion at high resolution, together with models of the forces behind it, could clarify how gene control works in time and what may go wrong when it fails. The work is mainly basic science and tool development.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yu Zhang
Michigan State University, MI·Microbiology & Immunology
Test whether cohesin-driven chromatin loop extrusion, in which DNA is pulled through cohesin to form loops, is required to bring distant V segments together with DJ segments for recombination at the IgH locus.
Jiang Wu
University of Texas Southwestern Medical Center, TX·Neuroscience
Determine how phosphorylation of BRG1, a chromatin remodeling protein, triggered by neuronal activity primes enhancers of activity-regulated genes by setting up a cohesin-dependent folding of chromosomes in 3D.
Danfeng Cai
Johns Hopkins University, MD·Biochemistry
Determine how RNA binding through RNA-recognition motifs, together with coiled-coil domains, drives the NONO-TFE3 and SFPQ-TFE3 fusion oncoproteins to form condensates in the nucleus.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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