Polly Morrell Fordyce

Quantifying protein unfolding kinetics with a high-throughput microfluidic platform

This paper introduces SPARKfold, a microfluidic platform to measure protein unfolding rates for thousands of variants, validating its accuracy and demonstrating its utility in studying kinetic stability.

Amplicon/Protein Bead Display enables quantitative in vitro biochemistry at scale

The paper introduces APB-Display, a method for high-throughput in vitro protein library production and analysis, quantifying binding affinities and expression levels of thousands of variants.

ADAPT-M: A workflow for rapid, quantitative in vitro measurements of enriched protein libraries

ADAPT-M rapidly quantifies protein binder affinities and kinetics using microfluidics, enabling efficient selection of high-affinity variants from yeast-display libraries.

uSort-M: Scalable isolation of user-defined sequences from diverse pooled libraries

uSort-M isolates and identifies protein variants from pooled libraries using automated sorting and long-read sequencing, achieving high recovery rates at lower cost.

Simple and Multiplexed Tracking of Bacterial Growth in Double Emulsion Droplets

This paper introduces a simple method to track bacterial growth in droplets over 12 hours, revealing growth rate heterogeneity not apparent in batch assays.

High-throughput biochemical phenotyping of SHP2 variants reveals the molecular basis of diseases and allosteric drug inhibition

This study uses high-throughput biochemical assays to analyze SHP2 variants, revealing that dysregulated autoinhibition drives disease and that allosteric inhibitors stabilize a partially active conformation.

FoTO1 orchestrates Taxol biosynthesis through catalytic and non-catalytic mechanisms

This paper identifies FoTO1 as a dual-function enzyme that enhances Taxol biosynthesis through catalytic conversion and non-catalytic organization of P450s in plants.

Engineering the mechanosensitivity of single DNA molecules via high-throughput microfluidic force spectroscopy

This study introduces SM3FS, a high-throughput microfluidic force spectroscopy method to analyze DNA mechanosensitivity, identifying structures that are kinetically stable but mechanically fragile.

Large field of view fluorescence imaging of microfluidic devices with a tandem-lens macroscope

This paper introduces a macroscope for wide-field fluorescence imaging in microfluidic devices, achieving high sensitivity and temporal resolution over a large area.

Continuous FACS sorting of double emulsion picoreactors with a 3D printed vertical mixer.

This paper improves the efficiency of FACS sorting of double emulsion picoreactors by optimizing surfactants and using a 3D-printed vertical mixer, achieving high accuracy and recovery in sorting.

Multiplexed perturbation of yew reveals cryptic proteins that enable a total biosynthesis of baccatin III and Taxol precursors

A multiplexed perturbation and single-nucleus RNA-seq screen of Taxus needles found eight new Taxol pathway genes, including FoTO1, enabling baccatin III and a late Taxol precursor in N. benthamiana.

Hydrophilic/ Omniphobic droplet arrays for high-throughput and quantitative enzymology

This paper introduces DA-MEK, a high-throughput platform for enzyme variant screening and kinetic analysis using droplet arrays, demonstrating accurate and efficient measurement of catalytic efficiencies.

High-throughput affinity measurements of direct interactions between activation domains and co-activators

This study quantifies direct interactions between 204 human activation domains and eight co-activators using a microfluidic platform, revealing 334 novel binding pairs and demonstrating the utility of analytical models for predicting activation.

De novo distillation of thermodynamic affinity from deep learning regulatory sequence models of in vivo protein-DNA binding

The paper introduces Affinity Distillation (AD), a method to extract thermodynamic affinities from deep learning models of in vivo TF binding, showing it outperforms motif-based methods in predicting sequence variation impacts.

Quantitative analysis of ZFY and CTCF reveals dependent recognition of tandem zinc finger proteins.

The paper quantifies how tandem zinc fingers in ZFY, CTCF, and ZNF343 recognize DNA motifs, showing dependent recognition and non-additive specificity.

Large-scale mapping and systematic mutagenesis of human transcriptional effector domains

The paper systematically maps and characterizes transcriptional effector domains in human chromatin regulators and transcription factors, identifying new activation and repression domains and their functional features.

uPIC-M: efficient and scalable preparation of clonal single mutant libraries for high-throughput protein biochemistry

The paper introduces uPIC-M, a method to efficiently create clonal single mutant libraries for high-throughput protein biochemistry, achieving high recovery rates and cost-effectiveness.

DeCoDe: degenerate codon design for complete protein-coding DNA libraries

DeCoDe optimizes degenerate codon libraries for protein-coding DNA, outperforming existing methods and supporting mixed-length libraries.

Satb1 integrates DNA sequence, shape, motif density and torsional stress to differentially bind targets in nucleosome-dense regions.

This study identifies factors that determine Satb1 binding-site selectivity, showing its preference for nucleosome-dense regions and its mechanosensitive interactions with DNA.

High-throughput chromatin accessibility profiling at single-cell resolution

The paper develops a high-throughput single-cell ATAC-seq method and applies it to cluster PBMCs by hematopoietic cell type.

Discovering epistatic feature interactions from neural network models of regulatory DNA sequences

The paper introduces DFIM, a method to identify epistatic feature interactions in neural network models of regulatory DNA sequences, validated on simulated and in vivo data.