Biology subjects

Winter, G.

Publications and source records attributed to Winter, G..

5 recordsLinked to original sources

bioRxiv2026

The Human Bindome: A Proteome-scale Atlas of Designed Binder Candidates

Affinity reagents such as antibodies are indispensable for interrogating proteins biological function. Yet they are costly and frequently unreliable, with unknown sequences, posing challenges to reproducible experimental research. Deep learning-based protein design can now in silico generate affinity reagents achieving reliable experimental success rates, but has remained largely confined to specialist laboratories. Here we present the Human Bindome, a proteome-scale atlas of high-confidence in silico protein binder candidates. By embedding the experimentally benchmarked BindCraft method in an accelerated, parallelized framework with automated domain-level target selection, we generated 306,146 binder candidates covering 8,296 human proteins (40.9% of the full proteome). Every candidate carries a defined sequence, a predicted binder-target structure model, and in silico confidence metrics. We characterize proteome-wide coverage and show that binder epitopes frequently overlap functional sites. This positions the Bindome as a resource of genetically encodable perturbagens for site-specific, modular control of protein function. The Bindome is freely available through a web interface (https://bindome.epfl.ch), with agentic, natural-language querying and as data splits for machine-learning model development. We anticipate that the Bindome will be valuable for the scientific community by providing affinity and perturbation reagents with broad applications in dissecting biological mechanisms as well as in drug and target discovery.

synthetic biology↗

bioRxiv2026

Induced Estrogen Receptor SUMOylation drives SERD activity

The ligand dependent transcription factor estrogen receptor (ER) is a key driver of and important drug target in breast cancer. Patients with advanced disease are typically treated with selective ER degraders (SERDs), whose therapeutic activity is commonly attributed to induced ER protein degradation. Yet the exact mechanism and relevance of degradation for clinical efficacy remain unclear. We show that SERDs directly induce ER SUMOylation, thereby triggering degradation via SUMO-targeted ubiquitin ligases (STUbLs). Inactivation of STUbLs prevents ER degradation and counterintuitively further sensitizes breast cancer cells to SERDs, rather than conferring resistance. SERD efficacy is independent of ER degradation, challenging the degradation-centric model of SERD action. Instead, SUMOylation recruits transcriptional co-repressors, turning SUMOylated ER into a dominant-negative repressor. Thus, SUMOylation rather than degradation is the direct consequence and driver of SERD activity. Our findings position SUMO-inducing drugs as a hitherto underappreciated yet clinically validated therapeutic modality with broad applicability.

Cancer Biology↗

bioRxiv2025

Phenotypic plasticity, heritability, and genotype-by-environment interactions in an insect dispersal polymorphism

Evolutionary fitness is determined by the match between an organisms phenotype and its local environment. When mismatched, individuals may disperse to more suitable habitats. For flightless insects, however, the range of dispersal is typically limited. Numerous flightless species have, therefore, evolved a dispersal dimorphism, that is, some individuals in otherwise short-winged populations develop long wings. Wing development may be genetically or environmentally determined, but these two drivers have rarely been analysed together. We studied the inheritance and density-dependent plasticity in the dispersal dimorphism of the meadow grasshopper Pseudochorthippus parallelus. Using a full-sib half-sib breeding design, we found that the development of long wings strongly depends on rearing density, with tactile stimulation being the most likely proximate cause. Additionally, we found heritable variation in the development of long wings, both in the propensity to produce long wings and in response to density (genotype-by-environment interactions). While at high and low densities, the environmental effect dominates, genetic variation takes effect mostly at intermediate densities. Our results have implications for the phenotype-environment match and ultimately the evolution of individualized niches. Induced dimorphisms represent a form of niche conformance (or adaptive phenotypic plasticity) and both genetic and induced dispersal dimorphisms facilitate niche choice in allowing individuals to sample a greater range of environments. Our study shows that niche-related polymorphisms can evolve via selection on the sensitivity threshold.

evolutionary biology↗

bioRxiv2022

xia2.multiplex: a multi-crystal data analysis pipeline

In macromolecular crystallography radiation damage limits the amount of data that can be collected from a single crystal. It is often necessary to merge data sets from multiple crystals, for example small-wedge data collections on micro-crystals, in situ room-temperature data collections, and collection from membrane proteins in lipidic mesophase. Whilst indexing and integration of individual data sets may be relatively straightforward with existing software, merging multiple data sets from small wedges presents new challenges. Identification of a consensus symmetry can be problematic, particularly in the presence of a potential indexing ambiguity. Furthermore, the presence of non-isomorphous or poor-quality data sets may reduce the overall quality of the final merged data set. To facilitate and help optimise the scaling and merging of multiple data sets, we developed a new program, xia2.multiplex, which takes data sets individually integrated with DIALS and performs symmetry analysis, scaling and merging of multicrystal data sets. xia2.multiplex also performs analysis of various pathologies that typically affect multi-crystal data sets, including non-isomorphism, radiation damage and preferential orientation. After describing a number of use cases, we demonstrate the benefit of xia2.multiplex within a wider autoprocessing framework in facilitating a multi-crystal experiment collected as part of in situ room-temperature fragment screening experiments on the SARS-CoV-2 main protease.

molecular biology↗

bioRxiv2020

Expression of TaTAR2.3-1B, TaYUC9-1 and TaYUC10 correlates with auxin and starch content of developing wheat grains

The role of auxin in developing grains of wheat (Triticum aestivum) is contentious with contradictory reports indicating either positive or negative effects of IAA (indole-3-acetic acid) on grain size. In addition, the contributions to the IAA pool from de novo synthesis via tryptophan, and from hydrolysis of IAA-glucose are unclear. Here we describe the first comprehensive study of tryptophan aminotransferase and indole-3-pyruvate mono-oxygenase expression during wheat grain development from 5 to 20 days after anthesis. A comparison of expression data with measurements of endogenous IAA via combined liquid chromatography-tandem mass spectrometry with heavy isotope labelled internal standards indicates that TaTAR2.3-1B, TaYUC9-A1, TaYUC9-B, TaYUC9-D1, TaYUC10-A and TaYUC10-D are primarily responsible for IAA production in developing grains. Furthermore, we show that IAA synthesis is controlled by genes expressed specifically in developing wheat grains as has already been reported in rice (Oryza sativa) and maize (Zea mays). Our results cast doubt on the proposed role of THOUSAND-GRAIN WEIGHT gene, TaTGW6, in promoting larger grain size via negative effects on grain IAA content. The work on TaTGW6 has overlooked the contribution of the dominant IAA biosynthesis pathway. Although IAA synthesis occurs primarily in the endosperm of wheat grains, we show that the TaYUC9-1 group is also strongly expressed in the embryo. Within the endosperm, TaYUC9-1 expression is highest in aleurone and transfer cells, supporting data from other cereals suggesting that IAA has a key role in differentiation of these tissues.

plant biology↗