Hologen

Symposium

The Hologen Symposium is a public event held during the first training week of the Doctoral Network. Project group leaders will present their perspectives on ongoing research in the field of hologenomics. The symposium will conclude with a roundtable discussion, offering an open forum to explore current and future opportunities that hologenomics presents for early-career researchers.

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Your data won't be made public. Registration includes coffee and snacks. Lunch is not included, but can be purchased at the canteen in the Mærsk Tower.

Agenda

Introduction to the HoloGen Doctoral Network, including aims, structure and planned activities.

The early-life microbiome plays a critical role in shaping host development, influencing immune programming, metabolism, and long-term health. This delicate ecosystem is a dynamic balance between beneficial microbes that support health and opportunistic pathogens that can drive disease. From maternal transmission at birth to environmental exposures in infancy, the infant hologenome undergoes rapid and complex shifts. In this talk, I will explore how beneficial microbes, including keystone species like Bifidobacterium, contribute to host resilience, while pathogenic and perturbed communities can disrupt early life health.

The human gut microbial community plays important roles in health and disease. Our gut microbes form complex interaction networks among each other and with their human host, which are still not well understood. Here, we study the interaction between two representative human gut bacteria, namely Roseburia intestinalis, a butyrate producer and next-generation probiotic candidate, and Bacteroides thetaiotaomicron, an abundant primary fermenter. Our work shows that gut bacteria have different strategies to deal with the challenges posed by their environment and that their interaction is highly context-dependent.

Gut microbiomes vary across space and time in response to environmental changes and internal microbial dynamics. These shifts are often correlated with host traits such as physiology, diet, and behavior. While observations in the wild can reveal such correlations, they cannot establish causality, as both microbiome composition and host traits may be influenced by confounding factors. Faecal microbiota transplants (FMTs) offer a promising experimental tool to manipulate microbiomes and assess their direct effects on host characteristics. In our research spanning mammals, reptiles, and amphibians, we explore both the potential and limitations of FMTs for uncovering causal relationships between gut microbiomes and host traits.

Both farmed and wild populations exhibit considerable variation in traits, often influenced by chemical pathways not directly encoded in their genomes; for example, methane emissions or ketosis in dairy cattle. Conventional quantitative genetics estimates the proportion of trait variation attributable to additive genetics (i.e., h² heritability) and predicts breeding values for selective breeding. However, the role of the holobiont is increasingly recognized as a key driver of host phenotypic variation. Foundational studies have shown that, for certain traits, the microbial community explains a significant portion of host phenotypic variation (m² microbiability), and some operational taxonomic units (OTUs) are themselves heritable. Additionally, some OTUs are significantly associated with host phenotypic variation. This raises an important question: Is an animal truly a holobiont if host genetics influence microbial abundance, which in turn affects trait variation? To explore this, we estimate microbiability and heritability separately for a given trait and then jointly to assess their relative overlap. This work will examine the current state of integrating quantitative genetics with holobiomics, discuss existing limitations, and highlight future research directions.

Hologenomics research involves complex data combinations encompassing various ‘omics technologies. Recent advances in statistical programming are now providing new solutions for open and collaborative methods development of data science methods and workflows. This talk will cover recent advances in this domain based on recent applications in microbiome population cohort studies, where generic data representations R/Bioconductor form the basis for a broader ecosystem of interoperable analysis and visualization methods.

It has been long known that there are regional differences in chronic disease risk, for example within Finland. The best way of exploring them is through a high-resolution grid independent of any regional borders. However, the number of disease events become sparse when the geographic resolution is increased. In order to control the inherent random noise, i.e. to find the signal from the noise, statistical methods are needed. This has led to the discipline of Bayesian disease mapping. I will present some case studies and methods and discuss how in the Hologenomics project we will adapt these methods to study the Geospatial variation in human hologenomics profiles in Finland.

Our team was part of a journey to reconstruct the three-dimensional genome of a woolly mammoth. Using paleo-Hi-C, we analyzed preserved DNA from a 52,000-year-old Siberian fossil and successfully mapped the mammoth’s genome in 3D. This revealed that woolly mammoths had 28 chromosome pairs, much like modern elephants, but with key differences in gene regulation. One of our most exciting findings was the identification of gene expression changes linked to cold adaptation, including those responsible for hair growth and fat storage. Remarkably, the chromosomes had remained intact for millennia due to a process called vitrification, which preserved the DNA in a glass-like state. We believe our study is more than just a breakthrough in paleogenomics—it offers a window into how extinct species adapted to their environments and how their genomes were regulated in life. Our work also demonstrates that difficult samples can be used for genomics and epigenomics.

Hologenomics is an emerging approach to understanding life by analysing the molecular components of both macroorganisms and their associated microorganisms as a unified system. The complexity of these biological systems, along with a lack of suitable tools, presents inherent challenges for researchers in the field. Yet, the hidden dynamics of host–microbiota interactions and the potential to refine our investigative methods offer rich opportunities for discovery. During the roundtable, we will explore these challenges and opportunities in conversation with four of the HoloGen group leaders, opening the floor for audience interaction and questions.

Speakers: 
Torgeir Hvidsten (NMBU, HoloGen coordinator), Leo Lahti (UTU, HoloGen training leader), Ostaizka Aizpurua (UTU, HoloGen research leader), Lindsay Hall (UB, HoloGen communication leader).