First, organize and label. Then, science.

Getting Strom Lab set up!

First day at my new job!
I'm a Lab Head, Principal Scientist in Discovery Oncology at Genentech.
I'll be searching for new targets to develop cancer treatments.

2nd photo is my newest friend on campus, decoy-ote.
@genentech.bsky.social

The HP1 and BRD4 chimeric constructs help us answer this-- if it were solely the denser placement of affinity polymer blocks, we'd expect the HP1-BRD4 construct (HP1's chromodomain + BRD4's IDR) to also engulf chromatin, but we find the opposite-- it can localize to HC but reduces chrom. density!

The structure of condensates and chromatin are interdependent.

Surface tension and stiffness– not just binding affinity or location– shape genome structure.

Elastocapillarity offers a physical basis for mesoscale nuclear morphology, with implications for gene regulation and disease.

Multiple types of condensates coexist within one nucleus, potentially interacting mechanically through modulating the chromatin network– we found that wetting condensates bundle and stiffen chromatin, constraining the size of non-wetting condensates.

We investigated the determinants of condensate wetting and chromatin stiffness in living cells.

Stiffness arises from chromatin density, while wetting is controlled by the strength and extent of chromatin binding, with heterochromatic protein HP1alpha’s chromodomain providing strong wetting

Elegantly, the variety of morphologies seen in nuclei can arise from varying just two parameters– condensate wetting and chromatin stiffness.

Nonwetting condensates in flexible networks cavitate and exclude fibers, while wetting condensates engulf and bundle them. Stiff networks inhibit growth.

Through simulations and experiments of a chromatin fiber networks and liquid-like condensates, we revealed that both chromatin-including, aspherical structures and chromatin-excluding, spherical structures seen in the mesoscale nucleus can be recreated through elastocapillarity

Liquid-fiber interactions– governed by the physical principle of elastocapillarity– are invoked when liquids adhere to flexible structures like membranes and microtubules. The liquid can influence the shape/structure of the fiber, and vice versa.

If heterochromatin is really a liquid-like condensate, why is it not spherical?
We investigated whether mechanical interactions between a condensate and a fiber network can explain the variety of morphologies seen in phase-separated nuclear compartments
www.biorxiv.org/content/10.1...