Biology subjects

Martini, G.

Publications and source records attributed to Martini, G..

8 recordsLinked to original sources

bioRxiv2025

Novel Fluorescent and Photoconvertible Fusions Reveal Dorsal Activator Dynamics

Over the last two decades, new in vivo and in cellulo imaging technologies have uncovered the inherently dynamic nature of transcriptional regulation in embryonic development and, in particular, in the fruit fly D. melanogaster. These technologies have made it possible to characterize the subnuclear and single-molecule dynamics of transcription factors. However, a lack of appropriate fluorescent protein fusions has, until now, limited these studies to only a few of the dozens of important transcription factors in the fruit fly gene regulatory network dictating early development. Here, we report the creation of four new fluorescent protein fusions to Dorsal, a member of the NF-{kappa}B/Rel family that initiates dorsal-ventral patterning. We generated and characterized two bright fluorescent protein fusions for Dorsal, meGFP and mNeonGreen, and two photoconvertible fluorescent protein fusions, mEos4a and Dendra2. We show that removal of the DsRed2 cassette commonly used to mark the CRISPR integration restores endogenous Dorsal mRNA and protein levels and enables the fusion allele to rescue a dorsal null allele, meeting the gold standard for endogenous function of a tagged protein in a fruit fly. We then demonstrate that our bright fluorescent protein fusions can be used to dissect the spatiotemporal dynamics of stable Dorsal clusters that traverse the nucleoplasm and uncovered that these clusters preferentially interact with active sites of Dorsal-modulated transcription. We further demonstrate that our photoconvertible fluorescent protein fusions make it possible to detect individual molecules of Dorsal in the nuclei of developing embryos. These new fluorescent protein fusions constitute a valuable resource for the community to elucidate the role of Dorsal activator dynamics in dictating fruit fly early embryonic development.

developmental biology↗

bioRxiv2025

Bridging data gaps: predicting inadequate micronutrient intake with machine learning

Identifying populations at risk of inadequate micronutrient intake is useful for governments and humanitarian organizations in low- and middle-income countries to make informed and timely decisions on nutrition relevant policies and programmes. We propose a machine-learning methodological approach using secondary data on household dietary diversity, socioeconomic status, and climate indicators to predict the risk of inadequate micronutrient intake in Ethiopia and in Nigeria. We identify key predictive features common to both countries, and we demonstrate the models transferability from one country to another to predict risk of inadequate micronutrient intake in contexts where nationally representative primary data are unavailable.

bioinformatics↗

bioRxiv2023

Temperature variation drives coordinated scaling of temporal and dynamic features of transcription in embryonic development

Temperature affects the timing of development in most poikilothermic organisms that cannot regulate their internal body temperature. In the fruit fly, Drosophila melanogaster, similar quantitative trends characterize changes in the timing of morphological events in embryogenesis from cellularization to hatching across a 10{degrees}C temperature range, such that the relative duration of each of these stages is temperature-independent. However, the extent to which the timing of the individual molecular and cellular processes underlying these morphological events recapitulates this relationship with temperature is largely unknown. Here, we characterized how the spatiotemporal dynamics of the process of transcription, which are so fundamental to cell fate commitment, scale with temperature in single cells of living fly embryos. Using the hunchback gene as a case study, we discovered that the duration of the cell cycle and the temporal and dynamic features of hunchback transcription scaled in a coordinated fashion such that the relative rates of all observed processes were temperature independent and, perhaps most surprisingly, such that the total amount of mRNA produced by the gene is unaltered by temperature changes. Our approach provides a crucial tool for understanding both developmental robustness in the face of environmental variation and for applying biochemical approaches in living Drosophila embryos.

developmental biology↗

bioRxiv2022

Optogenetic dissection of transcriptional repression in a multicellular organism

Transcriptional control is fundamental to cellular function. However, despite knowing that transcription factors can repress or activate specific genes, how these functions are implemented at the molecular level has remained elusive. Here we combine optogenetics, single-cell live-imaging, and mathematical modeling to study how a zinc-finger repressor, Knirps, induces switch-like transitions into long-lived quiescent states. Using optogenetics, we demonstrate that repression is rapidly reversible ([~]1 minute) and memoryless. Furthermore, we show that the repressor acts by decreasing the frequency of transcriptional bursts in a manner consistent with an equilibrium binding model. Our results provide a quantitative framework for dissecting the in vivo biochemistry of eukaryotic transcriptional regulation.

biophysics↗

bioRxiv2021

Antithrombin glycoforms from type II antithrombin deficient patients selectively adsorb onto the surface of plasma extracellular vesicles

Antithrombin (AT) is a glycoprotein produced by the liver and a principal antagonist of active clotting proteases. A deficit in AT function leads to AT qualitative deficiency, challenging to diagnose. Here we report that active AT may travel physiosorbed on the surface of plasma extracellular vesicles (EVs), contributing to form the "EV-protein corona". The corona is enriched in specific AT glycoforms, thus suggesting glycosylation to play a key role in AT partitioning between EVs and plasma. Differences in AT glycoform composition of the corona of EVs separated from plasma of healthy and AT qualitative deficiency-affected subjects were also noticed. This suggests deconstructing the plasma into its nanostructured components, as extracellular vesicles, could help to unravel pathophysiological mechanisms otherwise undiscovered.

biochemistry↗

bioRxiv2021

Cancer cells adapt FAM134B-BiP complex mediated ER-phagy to survive hypoxic stress

In a tumor microenvironment cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) which elicit unfolded protein response (UPR) as an adaptive mechanism. UPR activates autophagy enabling the degradation of misfolded/unfolded proteins. More recently, ER-specific autophagy has been implicated in the removal of damaged ER and restoration of ER-homeostasis. Our investigations reveal that during hypoxia induced ER-stress, the ER-phagy receptor FAM134B targets damaged portions of ER into autophagosomes to restore ER-homeostasis in cancer cells. Loss of FAM134B in breast cancer cells results in increased ER-stress and reduced cell proliferation. Mechanistically, upon sensing hypoxia activated proteotoxic stress, the ER chaperone BiP forms a complex with FAM134B and promotes ER-phagy. Our studies have further led to the identification of a pharmacological agent vitexin that disrupts FAM134B-BiP complex thereby inhibits ER-phagy and suppresses breast cancer progression in vivo.

cancer biology↗

bioRxiv2017

SelexGLM differentiates androgen and glucocorticoid receptor DNA-binding preference over an extended binding site

The DNA-binding interfaces of the androgen (AR) and glucocorticoid (GR) receptors are virtually identical, yet these transcription factors share only about a third of their genomic binding sites and regulate similarly distinct sets of target genes. To address this paradox, we determined the intrinsic specificities of the AR and GR DNA binding domains using a refined version of SELEX-seq. We developed an algorithm, SelexGLM, that quantifies binding specificity over a large (31 bp) binding-site by iteratively fitting a feature-based generalized linear model to SELEX probe counts. This analysis revealed that the DNA binding preferences of AR and GR homodimers differ significantly, both within and outside the 15bp core binding site. The relative preference between the two factors can be tuned over a wide range by changing the DNA sequence, with AR more sensitive to sequence changes than GR. The specificity of AR extends to the regions flanking the core 15bp site, where isothermal calorimetry measurements reveal that affinity is augmented by enthalpy-driven readout of poly-A sequences associated with narrowed minor groove width. We conclude that the increased specificity of AR is correlated with more enthalpy-driven binding than GR. The binding models help explain differences in AR and GR genomic binding, and provide a biophysical rationale for how promiscuous binding by GR allows functional substitution for AR in some castration-resistant prostate cancers.

systems biology↗

bioRxiv2016

The Tell-Tale Genome

Observable patterns of cultural variation are consistently intertwined with demic movements, cultural diffusion, and adaptation to different ecological contexts (Cavalli-Sforza and Feldman 1981; Boyd and Richerson 1985). The quantitative study of gene-culture co-evolution has focused in particular on the mechanisms responsible for change in frequency and attributes of cultural traits, on the spread of cultural information through demic and cultural diffusion, and on detecting relationships between genetic and cultural lineages. Here, for the first time, we make use of worldwide whole-genome sequences (Pagani et al. 2016) to assess the impact of demic diffusion on cultural diversity, focusing on the variability observed in folktale traditions (N=596) (Uther 2004) in Eurasia and Africa. We show that at small geographic scales (<=5000 km) there is a strong correlation between folktale and genomic distance when the effect of geography is corrected, while geographic distance has no independent effect on the distribution of folkloric narratives at the same spatial scale. This points to demic processes (i.e. population movement and replacement) as the main driver of folktale transmission at limited geographic ranges. The role of population movements becomes more apparent when regions characterized by episodes of directional expansions, such as the Neolithization of West Eurasia, are examined. Furthermore, we identify 89 individual tales which are likely to be predominantly transmitted through demic diffusion, and locate putative focal areas for a subset of them.

evolutionary biology↗