{"id":28476,"date":"2026-10-26T17:26:23","date_gmt":"2026-10-26T16:26:23","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/pavlo-hrab\/"},"modified":"2026-10-31T11:41:09","modified_gmt":"2026-10-31T10:41:09","slug":"pavlo-hrab","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/pavlo-hrab\/","title":{"rendered":"Pavlo hrab"},"content":{"rendered":"","protected":true},"featured_media":28477,"template":"","meta":{"_acf_changed":false},"university_us_portfolio":[29],"class_list":["post-28476","us_portfolio","type-us_portfolio","status-publish","post-password-required","hentry","university_us_portfolio-wageningen-university"],"acf":{"main_text":"","naam_van_het_proefschift":"Treasures of the deep:","samenvatting":"Het veld van natuurlijke producten begon met de ontdekking van penicilline en groeide uit tot een van de meest productieve pijplijnen in de moderne geneeskunde. Decennialang kwamen de meeste nieuwe antimicrobi\u00eble middelen van bacteri\u00ebn, maar de opkomst van antibioticaresistentie en een vertraging in de ontdekkingspijplijn dwongen tot nieuwe benaderingen. Vooruitgang in sequencing en computationele hulpmiddelen onthulden dat de chemische diversiteit in omgevingsgenomen veel groter is dan wat cultivatie ooit had aangetoond. Het probleem is echter dat deze microben vaak weigeren te groeien in een laboratoriumsetting.\n\nDit proefschrift pakt deze uitdaging aan door zich te richten op sponsen en de onderbelichte bacteriestam Acidobacteriota. In Hoofdstuk 1 wordt de geschiedenis van de ontdekking van natuurlijke producten geschetst, waarbij wordt betoogd dat de onbekende Acidobacteriota een ideale focus zijn voor toekomstig onderzoek. Hoofdstuk 2 brengt het biosynthetisch potentieel van de hele stam in kaart aan de hand van meer dan 19.000 genomen. De analyse toont aan dat mariene, gastheer-geassocieerde Acidobacteriota rijk zijn aan unieke genclusters voor de productie van gehalogeneerde metabolieten.\n\nHoofdstuk 3 onderzoekt de genomische kenmerken die gastheer-geassocieerde Acidobacteriota onderscheiden van vrijlevende varianten. Met behulp van machine learning worden specifieke kenmerken ge\u00efdentificeerd die wijzen op convergente evolutie naar een symbiotische levensstijl. Hoofdstuk 4 maakt de stap naar cultivatie door de diepzeespons Geodia barretti als model te gebruiken. Door genoomvoorspellingen te combineren met kennis over gastheermetabolieten (zoals taurine en carnitine), werd gepoogd dominante symbionten te isoleren. Hoewel negen nieuwe soorten werden ontdekt, bleven de meest dominante lijnen oncultiveerbaar, wat wijst op specifieke metabole afhankelijkheden zoals auxotrofie voor lysine en heem.\n\nHoofdstuk 5 concludeert dat de fylogenetische afstand tot bekende laboratoriumstammen de grootste hindernis vormt voor zowel functionele voorspelling als cultivatie. Het proefschrift positioneert de Acidobacteriota als een veelbelovende maar uitdagende groep voor de ontdekking van nieuwe medicijnen en benadrukt dat een iteratieve aanpak van voorspellen, testen en verfijnen essentieel is om deze 'schatten van de diepte' te ontsluiten.","summary":"The field of natural products began with the discovery of penicillin and grew into one of the most productive pipelines in modern medicine. For decades, most new antimicrobials came from bacteria. But antimicrobial resistance accelerated, and the discovery pipeline slowed. Nonetheless, advances in sequencing and computational tools eventually revealed that the chemical diversity encoded in environmental genomes far exceeds what cultivation had ever shown. The problem is that most of this diversity sits inside microbes embedded in complex microbiomes, and these microbes resist being brought into pure culture.\n\nThis thesis tackles that challenge from two angles: sponges, a rich source of marine natural products, and Acidobacteriota, an understudied phylum with known biosynthetic potential.\n\nChapter 1 traces the history of natural product discovery and microbiological research. Both began with cultivation, and for decades what could be grown set the limits of what could be found. Sequencing changed that, pointing to the vast biosynthetic potential locked in organisms no one has cultured. The chapter argues that abundant but undercultivated phyla like the Acidobacteriota are well placed to become the next focus of natural product discovery.\n\nChapter 2 surveys biosynthetic potential across the phylum. Drawing on comparative genomics and biosynthetic gene cluster analysis of more than 19,000 publicly available genomes and metagenome-assembled genomes, it maps BGC abundance and diversity across classes, families, and environments, and benchmarks Acidobacteriota against better-studied producer phyla. The analysis shows that biosynthetic potential is unevenly distributed within the phylum, with some clades rivaling canonical producers. Notably, the analysis shows that marine host-associated Acidobacteriota are enriched for clusters containing halogenase genes, including hybrid architectures with little similarity to any BGC previously characterized. This result sets up the rest of the thesis by singling out marine host-associated lineages as a promising place to look.\n\nChapter 3 zooms in on those marine host-associated lineages. Through comparative genomics of host-associated and free-living Acidobacteriota, it asks which genomic features distinguish the two. Using phylogenetically informed models and machine learning, it identifies features predictive of host association. Moreover, it highlights that host-associated lineages are distributed across the phylum rather than confined to a single clade. The chapter therefore treats host association less as a specific genomic signature than as a convergent outcome reached by distinct paths, and provides a set of candidate features that future work can test.\n\nChapter 4 shifts from prediction to cultivation. Using the deep-sea sponge Geodia barretti as a model, it tests whether combining host metabolomics with metagenomic predictions can improve the recovery of dominant symbionts, Acidobacteriota among them. Mining of the G. barretti microbiome points to slow-growing symbionts with unconventional substrate preferences, such as carnitine, creatinine, and taurine, which together motivate a targeted, oligotrophic media design and long cultivation times. The approach recovered substantial phylogenetic diversity, including nine previously undescribed species, but not the biosynthetically rich Acidobacteriota lineages predicted from the metagenomes. Pairing these isolation efforts with genome-scale metabolic models of the recovered strains offers a way to interpret the outcome, and to ask why the Acidobacteriota lineages may have escaped recovery.\n\nChapter 5 brings the threads together. It revisits the biosynthetic profiling of the phylum, the comparative genomics of host association, and the cultivation work as three complementary views on the same group of organisms. It argues that the same challenge runs through all three chapters. Predicting function, distinguishing lineages, and growing them are all made more difficult by the phylogenetic distance between Acidobacteriota and the cultured organisms our tools rely on. The chapter extends these lessons to the uncultivated majority more broadly, and sets out specific directions for tackling the challenge.\n\nTaken as a whole, the thesis positions Acidobacteriota as a promising group of natural product producers. It builds on earlier work to show where that potential is concentrated, then focuses on marine host-associated lineages and tests what it would take to bring them into culture. In doing so, it argues that Acidobacteriota are a useful entry point into broader questions in microbiome research.","auteur":"Pavlo hrab","auteur_slug":"pavlo-hrab","publicatiedatum":"12 november 2026","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/pavlohrabproof?iframe=true","url_download_pdf":"https:\/\/ebook.proefschriftmaken.nl\/download\/142b4e80-8186-4546-8e5d-0fafb0c7b765\/highres","url_epub":"","ordernummer":"19302","isbn":"","doi_nummer":"10.18174\/681758","naam_universiteit":"Wageningen University","afbeeldingen":28477,"video_url":"","podcast_url":"","naam_student:":"","binnenwerk":"","universiteit":"Wageningen University","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/28476","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/28477"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=28476"}],"wp:term":[{"taxonomy":"university_us_portfolio","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/university_us_portfolio?post=28476"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}