Florian Hollfelder

Deep generative embeddings of gene expression and splicing reposition the interpretation of single-cell transcriptomic signatures

Crecerelle integrates gene expression and alternative splicing to improve cell-type annotation and uncover regulatory pathways in single-cell transcriptomics.

Latent generative search unlocks de novo design of untapped biomolecular interactions at scale

Reward-guided inference-time search over the Proteína-Complexa sequence-structure codesign model yields validated binders across 127 targets, kinases and a free carbohydrate, with codesigned sequences outperforming ProteinMPNN redesign.

Epiblast Lumenogenesis is not a mammalian-specific trait

The paper shows that epiblast lumenogenesis occurs in veiled chameleons, a non-avian reptile, before anterior-posterior patterning, challenging the view that it is a mammalian-specific trait.

Unsupervised protein language models learn patterns of enzyme function

This paper introduces a framework using protein language models to discover novel enzymes with specific functions by clustering sequence embeddings and recursively exploring functional reservoirs.

A metagenomic thermostable monomeric meganuclease with novel specificity and unique palindromic 3-prime overhangs

The paper discovers a novel thermostable monomeric meganuclease from metagenomic data with unique DNA recognition and cleavage properties.

Oogenesis and germinal bed morphology of the brown anole (A. sagrei)

The paper describes 10 stages of oogenesis in the brown anole, showing conservation within iguanids and providing a framework for functional studies and gene-editing.

Studying the evolutionary potential of ancestral aryl sulfatases in the alkaline phosphatase family with droplet microfluidics

The paper uses droplet microfluidics to study the evolvability and robustness of ancestral and extant aryl sulfatases under varying mutation rates.

A portable dynamic loop module enables phosphotriesterase function in cysteine-dependent hydrolases

The paper identifies a novel phosphotriesterase from the DLH family and shows that loop flexibility influences activity, enabling engineering of higher activity in a human enzyme.

Pre-oviposition development of the brown anole (Anolis sagrei)

This study defines 26 developmental stages of pre-oviposition development in the brown anole, revealing divergence from chicken embryogenesis and providing insights into organ system morphogenesis.

Thermostable in vitro transcription-translation for enzyme screening in microdroplets

This paper develops a thermostable in vitro transcription-translation system using Thermus thermophilus extracts for enzyme screening in microdroplets.

Microdroplet screening rapidly profiles a biocatalyst to enable its AI-assisted engineering

The paper combines microfluidic screening with machine learning to rapidly engineer biocatalysts, achieving 23-fold improvement in catalytic efficiency through sequence-function mapping.

YeastIT: Reducing mutational bias for in vivo directed evolution using a novel yeast mutator strain based on dual adenine-/cytosine-targeting and error-prone DNA repair

YeastIT enables continuous in vivo protein evolution by reducing mutational bias and improving mutation rates compared to existing methods.

spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content

spinDrop improves single-cell sequencing by reducing noise and increasing detection rates, enabling high-quality molecular atlases of mouse brain development and organogenesis.

Expansion of novel biosynthetic gene clusters from diverse environments using SanntiS

This paper introduces SanntiS, a machine learning tool for identifying biosynthetic gene clusters in genomic and metagenomic data, and demonstrates its ability to predict a large number of novel BGCs with experimental validation.

Evolution of protease activation and specificity via alpha-2-macroglobulin-mediated covalent capture

This paper introduces a method to evolve protease activity and specificity using yeast display and alpha-2-macroglobulin-mediated covalent capture, demonstrating its application on six serine proteases.

Stem cell-derived mouse embryos develop within an extra-embryonic yolk sac to form anterior brain regions and a beating heart

This study shows that ETiX mouse embryos, generated from stem cells, develop through gastrulation and neurulation, forming anterior brain regions and a beating heart, and recapitulate natural embryonic development.

Gigavalent display of proteins on monodisperse polyacrylamide hydrogels as a versatile modular platform for functional assays and protein engineering

This paper introduces a modular platform using polyacrylamide hydrogel beads for protein display and functional assays, demonstrating enhanced potency through valency engineering.

A unified in vitro to in vivo fluorescence lifetime screening platform yields amyloid β aggregation inhibitors

The paper develops a unified in vitro to in vivo fluorescence lifetime screening platform to identify amyloid β aggregation inhibitors, revealing a new compound effective in multiple models.

Plakoglobin is a mechanoresponsive regulator of naïve pluripotency

This study shows that Plakoglobin regulates naive pluripotency in mouse ESCs through mechanosensitivity, with expression specific to the blastocyst stage in human and mouse embryos.

Droplet-based Single-cell Total RNA-seq Reveals Differential Non-Coding Expression and Splicing Patterns during Mouse Development

The paper introduces VASA-seq, a method for total single-cell RNA-seq in mice, revealing non-coding RNA expression and alternative splicing during development.

The proportion of periportal mesenchyme to ductal epithelial cells acts as a proliferative rheostat in liver regeneration

This study shows that the ratio of periportal mesenchyme to ductal epithelial cells regulates ductal cell proliferation during liver regeneration through Notch signaling.