Biology subjects

Jaremko, M.

Publications and source records attributed to Jaremko, M..

6 recordsLinked to original sources

bioRxiv2025

Probiotic and postbiotic treatment in situ during a marine heat wave improves coral health and promotes specific metabolic and microbiome changes

Microbial therapies are emerging as promising tools for coral protection against heat stress, yet such application was not tested in situ. We tested two coral-derived probiotic consortia and their heat-killed counterparts (postbiotics) on bleaching Acropora cf. valida in the Red Sea during a marine heatwave. Over 15 days, both live and one of the heat-killed treatments maintained photosynthetic efficiency (Fv/Fm), whereas placebo-treated corals exhibited significant thermal stress-induced decline. 16S rRNA gene sequencing profiling showed enrichment of putatively beneficial genera (e.g., Terasakiispira spp., Pseudoalteromonas spp.), and untargeted metabolomics resolved treatment-specific metabolic signatures that differed among consortia and between live and inactivated formulations. These molecular fingerprints illuminate specific underlying protective mechanisms and host-microbiome interactions under heat stress. Together, our results position microbial therapies (probiotics and specific postbiotics) as field-validated, mechanism-informed interventions capable of minimizing impacts on corals during real-world thermal extremes and provide design cues for scalable deployment.

microbiology↗

bioRxiv2024

Functional selection in SH3-mediated activation of the PI3 kinase

The phosphoinositide-3 kinase (PI3K), a heterodimeric enzyme, plays a pivotal role in cellular metabolism and survival. Its deregulation is associated with major human diseases, particularly cancer. The p85 regulatory subunit of PI3K binds to the catalytic p110 subunit via its C-terminal domains, stabilising it in an inhibited state. Certain Src homology 3 (SH3) domains can activate p110 by binding to the proline-rich (PR) 1 motif located at the N-terminus of p85. However, the mechanism by which this N-terminal interaction activates the C-terminally bound p110 remains elusive. Moreover, the intrinsically poor ligand selectivity of SH3 domains raises the question of how they can control PI3K. Combining structural, biophysical, and functional methods, we demonstrate that the answers to both these unknown issues are linked: PI3K-activating SH3 domains engage in additional "tertiary" interactions with the C-terminal domains of p85, thereby relieving their inhibition of p110. SH3 domains lacking these tertiary interactions may still bind to p85 but cannot activate PI3K. Thus, p85 uses a functional selection mechanism that precludes nonspecific activation rather than nonspecific binding. This separation of binding and activation may provide a general mechanism for how biological activities can be controlled by promiscuous protein-protein interaction domains.

biochemistry↗

bioRxiv2023

Learning from the expert: studying Salicornia to understand salinity tolerance

Salinity remains a major inhibitor of crop production in irrigated and marginal lands. The identification of genes involved in salinity tolerance has been predominantly limited to model plants and crop species. However, plants naturally adapted to highly saline environments can provide key insights into mechanisms of salinity tolerance. Plants of the genus Salicornia grow in coastal salt marshes, and their growth is even stimulated by NaCl - much can be learnt from them. We generated genome sequences of two Salicornia species and studied the transcriptomic and proteomic responses of Salicornia bigelovii to NaCl. Through the generation of subcellular membrane proteomes, we found that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, where it could be involved in mediating Na+ translocation into the vacuole to prevent toxicity in the cytosol. We identified 11 proteins of interest which, when expressed in yeast, altered salinity tolerance. One of these proteins, SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR showed it to be an intrinsically disordered protein and to localize to the endoplasmic reticulum in planta, where it could interact with ribosomes and RNA, potentially stabilizing or protecting them during salt stress. The study and understanding of the molecular mechanisms providing high salinity tolerance in S. bigelovii is likely to provide significant insights for improving salinity tolerance of crop plants.

plant biology↗

bioRxiv2020

Molecular Basis for the Adaptive Evolution of Environment Sensing by H-NS Proteins

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression, and hence toxicity and biological responses, to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less NMR spectroscopy and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the mechanism for H-NS-mediated environmental sensing and suggests that it resulted from the exaptation of an ancestral protein feature.

biochemistry↗

bioRxiv2018

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present manuscript, we developed a comprehensive next generation sequencing (NGS) panel which we applied on two different resources of FH in the Icelandic population: 62 subjects from 23 FH families with known or unknown culprit mutations, and a population-based sampling of 315 subjects selected for total cholesterol levels above the 95th percentile cut-point. The application of the NGS panel revealed significant diagnostic yields in identifying pathogenic LDLR mutations in both family and population-based genetic testing.

genetics↗

bioRxiv2018

Comprehensive Genetic Testing for Female and Male Infertility Using Next Generation Sequencing

ObjectiveTo develop a comprehensive genetic test for female and male infertility in support of medical decisions during assisted reproductive technology (ART) protocols.\n\nDesignRetrospective analysis of results from 118 DNA samples with known variants in loci representative of female and male infertility.\n\nInterventions(s)None\n\nMain Outcome Measure(s)Next-Generation Sequencing (NGS) of 87 genes including promoters, 5 and 3 untranslated regions, exons and selected introns. In addition, sex chromosome aneuploidies and Y chromosome microdeletions are analyzed concomitantly using the same panel.\n\nResultsAnalytical accuracy was >99%, with >98% sensitivity for Single Nucleotide Variants (SNVs) and >91% sensitivity for insertions/deletions (indels). Clinical sensitivity was assessed with samples containing variants representative of male and female infertility, and it was 100% for SNVs/indels, CFTR IVS8-5T variants, sex chromosome aneuploidies and Copy Number Variants (CNVs), and >93% for Y chromosome microdeletions. Cost analysis comparing the NGS assay with standard, multiple analysis approach, shows potential savings of $2723 per case. Conclusion: A single, comprehensive, NGS panel can simplify the ordering process for healthcare providers, reduce turnaround time, and lower the overall cost of testing for genetic assessment of infertility in females and males, while maintaining accuracy.

genomics↗