David Pincus

A DNA-barcoded Luria-Delbrück assay resolves mechanisms of adaptation

This paper introduces HiDenSeq, a DNA-barcoded Luria-Delbrück assay that uses deep sequencing to analyze adaptation mechanisms by resolving the Luria-Delbrück distribution over four orders of magnitude.

Cellquant: a vibecoder's guide to image analysis

One Python script, configured through LLM-assisted command-line calls, segments and quantifies 2D/3D multi-channel fluorescence images with provenance records; in a yeast temperature series it exposed a non-responding subpopulation.

A Statistical Approach to Cellular Resource Allocation Models

The paper uses statistical analysis to uncover growth tradeoffs in E. coli and S. pombe by identifying gene sectors and modeling transcription-translation constraints.

Chaperone condensates buffer the heat shock response against pleiotropic inputs

The paper shows that chaperone condensates specifically buffer the heat shock response, setting activation thresholds and ensuring specificity to heat shock in budding yeast.

Natural Selection in the Wake of Catastrophe

This paper develops a data-validated theory of natural selection after catastrophe, showing mean fitness relaxes inversely with time and follows Levenberg-Marquardt optimization in E. coli.

Mitochondrial respiration modulates Hsf1 activation and the heat shock response.

This study shows that mitochondrial respiration impairs Hsf1 activation and the heat shock response in yeast, with alternative chaperone programming compensating for reduced proteostasis.

Physiological architecture and evolutionary origins of cellular adaptability

The paper shows that cellular adaptability is shaped by evolutionary history through a prioritization hierarchy of transcriptional responses to environmental cues.

Organelles harbour pH gradients

The paper discovers pH gradients within organelles, challenging the assumption of uniform pH and prompting new questions about proton diffusion and its effects on organelle function.

Emergent 3D genome reorganization from the stepwise assembly of transcriptional condensates

The paper shows transcriptional condensates form stepwise in yeast to enable graded and 3D gene control during heat shock response.

Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response

This study identifies inducible transcriptional condensates in yeast heat shock response and shows they drive 3D genome reorganization through Hsf1-mediated gene coalescence.

ReporterSeq reveals genome-wide determinants of proteasome expression

ReporterSeq identifies Trr1 and ribosomal proteins as novel regulators of the UPS master regulator Rpn4 in yeast under stress conditions.

A dataset to explore kinase control of environmental stress responsive transcription

The paper presents a dataset analyzing kinase activity and gene expression in yeast under environmental stress, revealing how kinases modulate stress responses.

Heat Shock Factor 1 Drives Intergenic Association of Its Target Gene Loci Upon Heat Shock

This study shows that Hsf1 drives intergenic interactions of HSP gene loci in yeast during heat shock, forming subnuclear foci that dissolve with transcriptional attenuation.

Genetic and Epigenetic Determinants Establish a Continuum of Hsf1 Occupancy and Activity Across the Yeast Genome

The paper quantifies Hsf1 binding and transcription in yeast under basal and heat shock conditions, revealing a continuum of Hsf1 occupancy and activity across the genome.

Hierarchical organization endows the kinase domain with regulatory plasticity

This study reveals a hierarchical organization in the kinase domain that enables regulatory plasticity through distinct functional units.

Hsf1 phosphorylation generates cell-to-cell variation in Hsp90 levels and promotes phenotypic plasticity

The paper shows that Hsf1 phosphorylation creates cell-to-cell variation in Hsp90 levels, which enhances phenotypic plasticity in budding yeast.

Evolution and Engineering of Allosteric Regulation in Protein Kinases

The paper identifies and engineers phosphorylation sites on kinases to rewiring cell signaling through allosteric regulation.