Biology subjects

Andres, F.

Publications and source records attributed to Andres, F..

4 recordsLinked to original sources

bioRxiv2025

MdBRC1 and MdFT2 Interaction Fine-Tunes Bud Break Regulation in Apple

Winter bud dormancy is a critical adaptive process in temperate fruit trees, safeguarding meristems from freezing temperatures and aligning growth with seasonal cues. Dormancy encompasses two primary phases: endodormancy, where internal signals, particularly elevated abscisic acid (ABA), block growth and necessitate chilling for release; and ecodormancy, where buds regain growth competence but remain quiescent until external conditions are favourable. In apple (Malus domestica), we demonstrated that BRANCHED1 (MdBRC1) serves as a central inhibitor of bud growth specifically during ecodormancy. In many plant species, BRC1-like transcription factors integrate environmental and hormonal signals, activating gene networks linked to growth repression, notably those involved in ABA biosynthesis and signalling. Gain-of-function studies in poplar confirmed that MdBRC1 robustly suppresses shoot growth in trees. Our comparative transcriptomic analyses revealed that MdBRC1 directly regulates a suite of dormancy-associated genes, reinforcing its role as a molecular brake on bud break. Importantly, we show that the apple gene FLOWERING LOCUS T2 (MdFT2) is transcriptionally upregulated after dormancy and might act as a key inducer of bud break. Our data reveal that MdFT2 physically interacts with MdBRC1, reducing MdBRC1 activity during ecodormancy. This antagonistic interaction acts as a molecular switch, facilitating the transition from ecodormancy to active bud growth as spring approaches. Together, these findings uncover a regulatory module that finely tunes bud break timing in apple trees and provide a foundation for breeding strategies to enhance fruit tree resilience and adaptability in the context of climate change.

plant biology↗

bioRxiv2023

Cyclic peptide inhibitors stabilize Gq/11 heterotrimers

Heterotrimeric G proteins play a central role in cellular signaling, acting as switchable molecular regulators. Consequently, pharmacological agents to control G protein activity are of utmost importance to advance our understanding of this signal transduction system. The natural depsipeptides FR900359 (FR) and YM-254890 (YM) are two highly specific and widely used inhibitors of heterotrimeric Gq/11 proteins. These compounds have traditionally been understood to inhibit GDP dissociation by preventing the separation of the GTPase and -helical domains of the G subunit. In this work, we have determined the high-resolution crystal structures of FR and YM bound to heterotrimeric G11 and used them to explain the molecular basis underlying their efficient suppression of G protein signaling. Notably, our data show that FR and YM also function as stabilizers of the interface between the G and G{beta} subunits, acting as molecular adhesives that stabilize the entire heterotrimer. Our results reveal unrecognized mechanistic features that explain how FR and YM effectively blunt Gq/11 signaling in living cells.

biochemistry↗

bioRxiv2021

Unraveling the role of MADS transcription factor complexes in apple tree dormancy using sequential DAP-seq

BackgroundThe effect of global warming on dormancy and flowering patterns of crop trees threatens world-wide fruit production and food security. In Rosaceous tree species, it is believed that a group of genes encoding MADS transcription factors (TFs) controls temperature-mediated dormancy cycle. These genes are similar to SHORT VEGETATIVE PHASE (SVP) from Arabidopsis thaliana and referred as DORMANCY-ASSOCIATED MADS-BOX (DAM) genes. ResultsBy making use of apple tree (Malus x domestica) as a model for Rosaceous species, we have investigated the function of MADS TFs during the dormancy cycle. We found that MdDAM and other dormancy related MADS TFs form multimeric complexes with MdSVPa, and that MdSVPa is essential for the transcriptional complex activity. Then, for the first time in non-model plant species, we performed sequential DNA Affinity Purification sequencing (seq-DAP-seq) to define the genome-wide binding sites of these MADS TF complexes. Target genes associated with the binding sites were identified by combining seq-DAP-seq data with transcriptomics datasets obtained by the inducible glucocorticoid receptor expression system, and reanalyzing preexisting data related to dormancy cycle in apple trees. ConclusionWe have determined a gene regulatory network formed by MdSVPa-containing complexes that regulate the dormancy cycle in apple trees in response to environmental cues. Key genes identified with our genomic approach and the elucidated regulatory relationships provide leads for breeding fruit trees better adapted to changing climate conditions. Moreover, we provide novel molecular evidence on the evolutionary functional segregation between DAM and SVP proteins in the Rosaceae family.

plant biology↗

bioRxiv2021

waveRAPID(R) - a robust assay for high-throughput kinetic screens with the Creoptix(R) WAVEsystem

Surface-based biophysical methods for measuring binding kinetics of molecular interactions, such as Surface Plasmon Resonance (SPR) or Grating-Coupled Interferometry (GCI), are now well established and widely used in drug discovery. Increasing throughput is an often-cited need in the drug discovery process, and this has been achieved with new instrument generations where multiple interactions are measured in parallel, shortening the total measurement times and enabling new application areas within the field. Here, we present the development of a novel technology called waveRAPID for a further - up to ten-fold - increase in throughput, consisting of an injection method using a single sample. Instead of sequentially injecting increasing analyte concentrations for constant durations, the analyte is injected at a single concentration in short pulses of increasing durations. A major advantage of the new method is its ability to determine kinetics from a single well of a micro-titer plate, making it uniquely suitable for kinetic screening. We present the fundamentals of this approach using a small molecule model system for experimental validation and comparing kinetic parameters to traditional methods. By varying experimental conditions, we furthermore assess the robustness of this new technique. Finally, we discuss its potential for improving hit quality and shortening cycle times in the areas of fragment screening, low molecule weight compound screening, and hit-to-lead optimization.

biophysics↗