@ECosta173

PhD candidate @Stanford Biology in @BintuLab interested in systems and synthetic biology | Previously @Princeton Physics

 Stanford, CA
Joined October 2022
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Numerous biotech innovations started with adapting a protein to its non-native context, which often requires substantial experimental optimizations. Here’s a breakdown by our lead, @Xiaowei0402, on a versatile, efficient computational framework to facilitate such adaptations.
Xiaowei Zhang
@Xiaowei0402Oct 20
We deimmunized a clinical CD19 CAR binder with experimentally detected HLA-I epitope depletion while retaining tumor killing, and rescued a secreted protease to function in the cytosol. Both done with one unified design framework: ProVADA. How it works and what we tested 🧵 (1/11)
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Excited to share some recent collaborative work between the Bintu and Ferrell labs investigating single-cell and population-level transcriptional response functions in minimal mammalian expression systems! biorxiv.org/content/10.64898…

Stable epigenetic states set single-cell activation thresholds in mammalian expression systems

Quantitatively relating transcription factor (TF) input to gene expression output is central to understanding mammalian gene regulation and essential for designing predictable synthetic expression...

biorxiv.org
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Different activation domains from different transcription factors can independently regulate activation thresholds and expression levels once active, but this relationship is fixed for a single AD (like VP48). Some ADs can drive unimodal expression at varying levels.
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We think that these results help advance our understanding of how TFs interact with chromatin to modulate features of transcriptional responses, and hopefully provide some design considerations or engineering strategies for researchers using these inducible expression systems!
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We just finished writing up this beautiful story on how transcription factors can generate pulses by using chromatin (led by Cece & @ECosta173 ): Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-dependent manner biorxiv.org/content/10.64898…

Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-depe...

Dynamic gene expression pulses enable adaptive response to stimuli and can be generated in natural and synthetic systems. Controlling these dynamics typically involves circuits consisting of multiple...

biorxiv.org
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Eli Costa retweeted
Bintu Lab@BintuLab17 Oct 2023
We’re excited to announce our new preprint, ‘The H3.3 K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation,’ expertly led by graduate student @sinha_joydeb! (1/9) biorxiv.org/content/10.1101/…

The H3.3 K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA...

Histone H3.3 is frequently mutated in cancers, with the lysine 36 to methionine mutation (K36M) being a hallmark of chondroblastomas. While it is known that H3.3K36M changes the cellular epigenetic...

biorxiv.org
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New preprint! We studied how single-cell 3D chromatin structure changes under targeted epigenetic perturbations using multiplexed DNA FISH and synthetic biology tools, and found an intriguing relationship between chromatin compaction and epigenetic memory. biorxiv.org/content/10.1101/…

Single-cell chromatin state transitions during epigenetic memory formation

Repressive chromatin modifications are thought to compact chromatin to silence transcription. However, it is unclear how chromatin structure changes during silencing and epigenetic memory formation....

biorxiv.org
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A life spent at the roots: rdcu.be/dlCTg Joaquín Hortal reviews @JimCostaHBS's new biography of Alfred Russel Wallace
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