For many scientists, Bork was above all a pioneer who helped establish computational biology as a major discipline in the life sciences. For those who worked alongside him more closely, he was something more personal: a mentor and manager, a collaborator, a scientific compass, and a friend. His influence shaped not only entire research fields but also the intellectual journeys and careers of generations of scientists, many of whom now lead laboratories and companies across the world.

Bork’s scientific career was remarkable in its breadth, its depth, and his foresight regarding future developments in biology. Born in 1963 in the former East Germany, he began his scientific life working with Jens Reich in Berlin at the Central Institute for Molecular Biology of the Academy of Sciences of the German Democratic Republic, where he completed his PhD research in biochemistry. It was an unusual starting point for someone who would go on to become one of the most influential figures at the intersection of biology and computation, but it instilled in him an early appreciation for rigorous, quantitative thinking applied to living systems.

Following Germany’s reunification in 1990, Bork moved quickly. In 1991, he joined the European Molecular Biology Laboratory in Heidelberg with an EMBO fellowship, working with Chris Sander. In doing so, he entered a research environment he later referred to as uniquely enabling, providing fertile ground for his talent and vision to pursue a seamless interdisciplinary integration of biology and computation. Over more than three decades at EMBL, he produced groundbreaking science and contributed substantially to shaping the institution itself. He served for many years as Head of the Structural and Computational Biology Unit, later became Director of EMBL Heidelberg, and thereafter served as EMBL’s Interim Director General.

His scientific contributions spanned an extraordinary range of topics, including genome analysis, protein function and structure prediction, protein interaction networks, drug–target relationships, microbiome research, evolutionary biology, and planetary biology. Among many seminal contributions, Bork played a key role in developing computational approaches for predicting protein function and interaction networks, as well as for the analysis of metagenomes, the complete collection of genetic material from all organisms in a given environmental sample. These methods transformed how researchers extract biological meaning from the flood of sequence data generated by modern genomic technologies, turning raw information into testable hypotheses about how proteins work, how they interact, and how organisms relate to one another.

Bork’s scientific curiosity rarely stopped at the established boundaries of fields. Long before research on microbiomes became mainstream, he recognised the immense biological and medical importance of microbial communities. He helped demonstrate that microbiomes are not merely collections of microorganisms but dynamic ecosystems that influence environmental processes and human health. His work identifying gut microbial community structures, so-called enterotypes, changed how scientists conceptualise microbial variation among individuals, suggesting that human gut communities fall into recognisable patterns with potential consequences for health and disease. His contributions to disease research using microbiome analysis were equally remarkable: by identifying microbial markers associated with conditions such as colon or pancreatic cancer and obesity, his research helped open new avenues for diagnostic and therapeutic exploration.

One of his most inspiring initiatives was the Traversing European Coastlines, or TREC, project, an initiative that drew inspiration from the Tara Oceans project, in which Bork had been involved from the very beginning. TREC brings together scientists from diverse disciplines to systematically study Europe’s coastal ecosystems while also engaging the public in scientific discovery. Bork designed, kick-started, and led TREC as its scientific director until his recent passing. He often drew parallels between ecological and microbial communities, seeing both as interconnected systems whose complexity demands collaborative exploration to gain a better understanding of our planet. Today, the analysis of thousands of samples generated through the TREC project continues as part of his enduring legacy, a reminder that the scientific programmes he built were designed to outlast any single career.

Bork’s achievements were recognised globally. He received numerous prestigious awards, including the Novozymes Prize, the ISCB Accomplishments by a Senior Scientist Award, and the Royal Society and Académie des Sciences Microsoft Award. He was elected to Germany’s National Academy of Sciences, to EMBO, and to the Academia Europaea, and he held honorary doctorates and professorships across Europe and Asia. He served on the editorial boards of numerous scientific journals, including the board of reviewing editors of Science and the Editorial Board of Cell, and was one of the founding editors of Molecular Systems Biology. He secured two ERC Advanced Grants and co-founded several successful biotech companies. Yet, despite this extraordinary list of honours, it became clear from his interactions with colleagues that what he was most proud of was his science and, above all, the people around him, including the young scientists he advised and his collaborators.

Bork had a remarkable ability to identify potential in young scientists, often before they recognised it themselves. He encouraged intellectual risk-taking and fostered an environment in which curiosity was valued over convention. He reminded students, postdocs and colleagues to pursue the most meaningful questions rather than the safest or most fashionable ones. For him, mentoring was not simply about completing projects but about enabling young researchers to develop independent scientific identities. Alumni from his group felt this connection for many years; he took great pride in staying in touch with them, often speaking about their successes and inviting them to join him at scientific meetings long after they had established independent careers. The success of this philosophy is evident in the many scientists who trained under him and later assumed leadership roles across academia and industry. His mentorship was formally recognised with the Nature Award for Creative Mentoring in 2008.

His approach to science was deeply intertwined with his personality. He embodied the philosophy of work hard and play hard in the truest sense, being both a competitive scientist and an enthusiastic gamer. At EMBL, his research group became notorious for dedicated computer gaming sessions right after lunch, with Bork often right in the middle of the action. Colleagues recall the joy in his eyes when he won a computer game, often succeeding in situations that at first seemed hopeless, and later taking pleasure in talking through what allowed him to secure his win with the lab. These characteristics reflected his scientific spirit: a constant desire to explore novel data types, to push established field boundaries through landmark publications, to refine scientific narratives until they got the point right, and ultimately to take his research where no one had gone before. Beyond his own laboratory, Bork had a remarkable ability to build collaborative communities, seeing EMBL not merely as an institution but as a living network of people united by curiosity and shared purpose. His legacy is visible everywhere: in the tools and databases scientists use every day, in the conceptual frameworks guiding systems biology and microbiome research, and in the collaborative and interdisciplinary ethos at EMBL. Bork often emphasised that science is a collective and generational endeavour, and in that sense his work continues, in the people he inspired and through the collaborations he nurtured. His absence will be felt for many years to come, but his influence on science, on EMBL, and on the many people whose careers he shaped will endure far longer.

Subject of Research: The life, career and scientific legacy of computational biologist Peer Bork

Article Title: Scientific obituary: Peer Bork

Article References: Korbel, J. O. (2026). Scientific obituary: Peer Bork. Molecular Systems Biology, 22(5), 621-623. https://doi.org/10.1038/s44320-026-00204-x

Image Credits: AI Generated

DOI: 10.1038/s44320-026-00204-x

Keywords: Peer Bork, computational biology, EMBL, microbiome, enterotypes, metagenomics, protein interaction networks, TREC, Tara Oceans, mentorship, systems biology, bioinformatics

Sperm motility, the capacity of sperm cells to navigate through the female reproductive tract towards the oocyte, is fundamental for successful fertilization. Despite decades of research, the intricate protein networks orchestrating this motility remain only partially mapped. The axoneme, a highly conserved microtubule-based structure forming the skeleton of eukaryotic cilia and flagella, houses a myriad of proteins critical to flagellar beating and energy transduction. CFAP91—Cilia and Flagella Associated Protein 91—has been identified previously as a scaffolding component within the axoneme, but its interactome and functional partners in sperm remained largely unknown.

Leveraging a proximity-dependent biotin identification technique—proximity labeling—researchers were able to go beyond traditional protein interaction studies. This method allows for the tagging of proteins that lie in the immediate vicinity of a bait protein under physiological conditions, providing a refined snapshot of protein neighborhoods within complex structures like the axoneme. CFAP91 was used as the bait, and by fusing it with an engineered enzyme that biotinylates nearby proteins, the team successfully captured a dynamic interactome within sperm flagella.

Among the proteins identified, EFCAB5 (EF-hand Calcium Binding domain 5) stood out due to its unique domain architecture and its potential calcium regulation capability. Calcium ions have long been implicated in modulating flagellar beating patterns, yet how specific calcium-binding proteins integrate into the axonemal framework has remained speculative. EFCAB5’s designation suggested a pivotal role in sensing or transducing calcium signals necessary for motility regulation.

Subsequent functional characterization using gene-editing techniques in murine sperm elucidated the essentiality of EFCAB5 for proper flagellar function. Loss of EFCAB5 led to severely impaired sperm motility characterized by erratic and non-progressive movement patterns. High-speed video microscopy and subsequent kinematic analyses revealed that the absence of EFCAB5 disrupted the fine-tuned coordination of axonemal components that produce symmetrical and well-tempered flagellar waves. This deficient motility phenotype closely mirrors clinical characteristics observed in certain cases of idiopathic male infertility.

The mechanistic investigation extended to decipher how EFCAB5 interacts with CFAP91 and other axonemal proteins. Co-immunoprecipitation assays, combined with in situ proximity ligation, confirmed a physical and functional coupling between EFCAB5 and CFAP91 within the radial spoke complex—a critical regulator of flagellar beat frequency and amplitude. This suggests that EFCAB5 functions as a crucial calcium sensor or modulator that influences axonemal mechanics via CFAP91, thus directly impacting the physical forces driving sperm progressivity.

Notably, calcium regulation in flagella is a rapidly reversible and highly localized process, critical for enabling sperm to adjust their motility patterns in response to chemical and mechanical cues encountered during their journey in the female reproductive tract. EFCAB5’s ability to bind calcium via its EF-hand domains likely positions it as a molecular switch modulating conformational changes in the axoneme, thereby translating transient calcium fluxes into mechanical output. Such nuanced regulation extends our conceptual framework of how local signaling cascades integrate with cytoskeletal dynamics to generate motility.

From a methodological perspective, the success of proximity labeling in dissecting the axonemal proteome underscores the power of innovative biochemical tools to map organelle-specific interactomes. Traditional co-immunoprecipitation approaches often fall short due to the insolubility, low abundance, or transient interactions of key axonemal proteins. Proximity labeling overcomes these limitations, facilitating a more comprehensive and physiologically relevant portrait of protein-protein networks, especially in structurally intricate systems like sperm flagella.

This discovery also holds clinical implications. Male infertility affects approximately 7% of men worldwide, and in nearly half of these cases, sperm motility defects are the underlying cause. Identification of EFCAB5 as a crucial regulator invites exploration of its genetic variants among infertile men. Screening for mutations or dysregulation of EFCAB5 could complement current diagnostic paradigms, offering a molecular target for personalized assessment and possibly therapeutic modulation.

Moreover, understanding how EFCAB5 orchestrates calcium-mediated signaling to govern flagellar dynamics may inspire novel fertility treatments aimed at restoring or enhancing sperm motility. Pharmacological agents or gene therapies designed to modulate EFCAB5’s function could become a reality, presenting alternatives to assisted reproductive technologies that bypass—but do not address—the motility deficits.

Expanding the scope, this study also contributes to the broader field of cilia and flagella biology. Given that ciliary dysfunction underpins a host of human diseases collectively termed ciliopathies—with manifestations spanning respiratory, renal, and neurological deficits—the principles learned from EFCAB5’s role in sperm flagella may have wider relevance. Similar calcium-dependent regulatory mechanisms might exist in other motile cilia, revealing broader biological paradigms and therapeutic opportunities.

Structurally, EF-hand motifs exemplify versatile calcium-binding domains found across various proteins involved in signal transduction and cytoskeletal regulation. EFCAB5’s localization within the highly specialized confines of the radial spoke complex suggests a finely adapted function integrating calcium sensing with mechanical modulation. This attests to the evolutionary refinement of motility regulation in cells where precision and responsiveness are paramount.

Future lines of investigation will likely explore the dynamic interplay between EFCAB5 and other calcium-binding proteins within the axoneme, elucidating how combinatorial interactions and post-translational modifications influence sperm motility patterns under physiological and pathological conditions. Integrating high-resolution cryo-electron microscopy with live-cell imaging and proteomics could provide unprecedented insights into these processes.

In conclusion, the identification of EFCAB5 as a key regulatory protein for sperm motility marks a seminal advance in reproductive biology. By harnessing proximity labeling centered on CFAP91, the research team unlocked new dimensions in our understanding of the molecular machinery driving sperm function. Beyond male infertility, these findings ripple across the fields of cell motility, calcium signaling, and organelle biology, reinforcing the centrality of precise protein networks in cellular function.

The impact of this work extends into translational realms, offering hope for novel diagnostics and treatments tailored to combat male infertility. Furthermore, the methodological innovations exemplified herein stand as a beacon for future studies investigating complex protein-interaction landscapes within challenging cellular environments. As we venture deeper into the nanoscale choreography of sperm flagella, insights such as those revealed by EFCAB5 promise to illuminate fundamental principles sculpting life’s earliest moments.

Subject of Research: Sperm motility regulation via axonemal protein interactions and calcium signaling.

Article Title: Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility.

Article References:
Wang, H., Shimada, K., Pham, A.H. et al. Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility. Nat Commun 16, 8238 (2025). https://doi.org/10.1038/s41467-025-63705-7

Image Credits: AI Generated