Our research featured in Quanta Magazine

Microbiologists are searching for a universal theory of how bacteria form communities based not on their species but on the roles they play.

A new article in the popular science magazine Quanta has highlighted our work on metabolic preferences and their genomic markers. How can we identify rules of microbial communities? What are the traits that determine success in a community? What level of abstraction is useful when thinking about the many species of bacteria living in a given community? How can we design microbial consortia? These are some of the questions that the research (including our own) described in this article is trying to unravel. Exciting times for microbial ecology!

Read the article here: https://www.quantamagazine.org/the-quest-for-simple-rules-to-build-a-microbial-community-20240117/

Herwig to lead €5M NWO Perspective Grant Consortium for plant-based fermentations

The Netherlands Organisation for Scientific Research (NWO) granted the FERMI Perspective proposal led by Herwig Bachmann from the Systems Biology Lab. The project aims to accelerate the protein transition by improving the taste of plant-based products through fermentation by microbes. With colleagues from the Wageningen University and TU Delft and 10 industrial partners, the project will combine experimental and computational methods to unravel the biochemistry of the underlying conversions: which chemistry, enzymes and pathways turn beany and grassy flavours into meaty or neutral ones? This knowledge should accelerate a shift towards a more plant-based diet and will contribute to a more sustainable food production chain.

For more info, see the infographic below (click to enlarge).

Overview over the FERMI project

New paper: Genome content predicts the metabolic preferences of bacteria

Bacteria grow in communities of many co-occurring species in , e.g., in your gut, in soil, or in the ocean. A fundamental process in these communities (more specifically, communities of heterotrophic bacteria, i.e., bacteria that utilize organic carbon sources) is that bacteria take up substrates (basically, food) like sugars and amino acids from the environment and turn them into biomass or convert them into something else they then excrete. For this new paper, what we wanted to know was: which substrates can different bacteria use (we were focused on substrates they can use as a carbon source)? Can we identify patterns of substrate utilization, e.g., are similar compounds consumed by similar bacteria? Can we predict these patterns by looking at which genes different bacteria encode? Our work touches on several important questions in microbiology, from microbial ecology (how do microbial communities work?) to biochemistry (how does the structure of metabolic pathways shape substrate utilization patterns?) to genomics & evolution (how are capabilities of substrate utilization encoded in the genome, and how did evolution shape these genomic patterns?).

High-throughput growth characterization workflow used in this project

By analyzing the growth of 182 different strains of marine bacteria on 135 different potential carbon sources, we found that we can describe the substrate preferences of our bacteria to a first approximation in terms of their preference for sugars (e.g., glucose or polysaccharides like starch) relative to acids (e.g., amino acids or organic acids which are important intermediate during the chemical conversion of substrates into biomass). This preference is encoded in the genomes of bacteria, which tells us about the evolution of these preferences, but also makes the preferences predictable from genomes.

Analysis of growth phenotypes shows that the main discriminatory characteristic between species is the degree to which they prefer sugars or acids.

Our work reveals a way to simplify how we think about the metabolic capabilities of bacteria: we can describe a given heterotrophic bacterium by its degree of specialization along the axis of sugar to acid specialists. This is very useful because it allows us to describe communities of bacteria in a simple way (e.g., by their collective degree of specialization). More fundamentally, our work also shows how the evolution of bacterial genomes is structured by biochemical constraints which drives bacteria to specialize along this axis of sugar to acid specialists. Since the metabolic preferences are encoded in genomes, we can estimate the metabolic capabilities of species that we have not (yet) cultured, but for which we have genomic information (e.g., by sequencing entire communities and piecing together the genomes of the constituent species, a process called metagenomics). This allows us to begin to understand the metabolic processes in many microbial communities in the environment in a simplified manner.

Through evolution, species may be selected to specialize in either glycolysis or gluconeogenesis. This saves them from having to switch directions often as environmental conditions change (which is expensive), but this reduces their metabolic adaptability, which may be bad in fluctuating environments.

Out now: Genome content predicts the carbon catabolic preferences of heterotrophic bacteria

New paper: Lifestyle influences microbiome

In primate species, a change in lifestyle leads to adjustments in their microbiome. What does this mean? 

The study subject, the ARTIS gorilla Akili

Over the last years, ARTIS Micropia Professor Remco Kort and his Bioinformatics & Systems Biology student Isabel Houtkamp studied the faeces of the western lowland gorilla. They did this by comparing the composition of the microbiome of the ARTIS gorillas with that of their wild counterparts – and also with that of humans. They were assisted by Walter Pirovano and Mark Bessem of the company BaseClear, experts in the field of microbial DNA analyses. This research revealed interesting correspondences. In both primate species, a change in lifestyle led to adjustments in their microbiome. So what does this mean? 

To find out, check out their new paper here and a behind-the-scenes story Remco wrote for Micropia.

Summary of Planetary Health meeting published

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A new network of over 72 organizations from 12 countries was activated during a convening at ARTIS in Amsterdam on 26–27 September 2022, organized by Remco Kort. Representatives are aligned with the transdisciplinary field and social movement of Planetary Health, which analyzes and addresses the impacts of human disruptions to natural systems on human health and all life on Earth. The new European Planetary Health Hub consists of organizations from various sectors, including universities, healthcare, youth, business, and civil society. The Convening, co-organized by the Planetary Health Alliance (PHA), the European Environment and Sustainable Development Advisory Councils Network (EEAC), and Natura Artis Magistra (ARTIS), aimed to develop Planetary Health Working Groups for Education, Policy Engagement, Research, and Movement Building. The Convening resulted in an outline for each of the Working Group’s aims, visions, missions, priorities, and activities, and set the framework for sustaining their activities in the future through the establishment of the European Planetary Health Hub Secretariat in the Netherlands. The Hub members shared lessons learned, built relationships, and developed artwork-inspired perspectives on Planetary Health. In conclusion, the Convening led to the establishment of a strong European foundation to contribute to the transformations needed for sustainable, just, and equitable societies that flourish within the limits of our ecosystems. The conclusions of the meeting are now published in Challenges.

For more information on the meeting, see VU News and read the meeting summary paper.

New perspective on principles in microbial ecology published

Microbial communities play pivotal roles in ecosystems across different scales, from global elemental cycles to household food fermentations. These complex assemblies comprise hundreds or thousands of microbial species whose abundances vary over time and space. Unraveling the principles that guide their dynamics at different levels of biological organization, from individual species, their interactions, to complex microbial communities, is a major challenge. To what extent are these different levels of organization governed by separate principles, and how can we connect these levels to develop predictive models for the dynamics and function of microbial communities?

In a new perspective piece, Matti discusses recent advances that point towards principles of microbial communities, rooted in various disciplines from physics, biochemistry, and dynamical systems. By focusing on principles that transcend specific microbiomes, we can pave the way for a comprehensive understanding of microbial community dynamics and the development of predictive models for diverse ecosystems.

“Searching for Principles of Microbial Ecology Across Levels of Biological Organization” is now published in Integrative and Comparative Biology (https://academic.oup.com/icb/advance-article/doi/10.1093/icb/icad060/7191255)

Maarten won a poster prize and acquired a fresh, new pair of red socks!

PhD candidate Maarten Droste is one of the recipients of the famous Red Sock Award for best poster presentation at the SIAM 2023 Conference on Applications of Dynamical Systems in Portland, Oregon. It is a tradition that each prize winner receives a pair of red socks as part of the award. His winning poster, entitled “Determinants of optimal metabolic pathway choice by microorganisms”, is co-authored by Bob Planqué and Frank Bruggeman. 

Maarten’s PhD project is all about understanding the key features and determinants of metabolic pathways choices by microorganisms, using optimality principles and mathematical models.

One of his first results is that physical systems that are alive may obey different principles than those that are inanimate. Whereas inanimate systems generally have increased fluxes (J) at higher thermodynamic driving forces (X) and therefore have a higher entropy production rate (approx. J times X), living systems may adjust their metabolism at higher nutrient concentrations in such a way that the driving force reduces but the flux – which is what matters for cell – still increases, because they swap longer for shorter pathways that only partially degrade the nutrient(s). They do this because enzyme concentration inside cells are bounded and a shorter pathway allows them to have higher enzyme concentration per reaction, and therefore a higher flux. Thus, natural selection of living microbes for growth rate that does not necessarily lead to higher entropy production, as is sometimes stated.

Another one of his findings is that optimal pathway choice depends on the concentrations of nutrients and products of metabolism. And, therefore, on the characteristics of their biotic and abiotic environment.

The abiotic effect is that the nutrient and product concentrations at the cell’s surface matter for the metabolic flux, which are determined by their values at “infinity”, diffusion coefficients, and the rates of cellular metabolism. Since the rates of cellular metabolism contribute to setting those concentrations, metabolic pathway optimization should be done with nutrient and product diffusion incorporated into the nonlinear optimization problem. Maarten has worked out this fundamental problem.

An important biotic effect also plays a role: The concentrations at the cell’s surface are also determined by the activity of other microbial species, and their relative distances, indicating that ecology matters too! Here Maarten has stumbled on a curious finding when the concentration of a product is low enough, a long pathway can have outperform a shorter pathway – even though the long pathway has lower enzyme concentrations per reaction. Whether this happens depends on the kinetics and abundance of nearby microbes feeding on this product. Thus, microbes together shape their “niche”, affecting their optimal pathway choices!

Maarten will be continuing his scientific adventures, wearing his fresh new pair of red sox!

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Lab retreat in Berg en Dal

After a few years break, finally it was again time for a lab outing. In the lovely setting of Berg en Dal, we enjoyed three days (April 19th-21st) of networking and conviviality.

“Mens sana, in corpore sano” they say, so we stretched both our muscles, with plenty of biking, jeu de boules, ping pong and football, and also our brains, with the Pub Quiz and Board Games nights.

Multicultural foods and drinks (Italian and Chinese dinners, Dutch lunch and snacks, Lithuanian schnaps,…) provided the right amount of energy.

But there no real fun without some sciency science. We discussed and practised together how to effectively pitch our research interests and ideas. To practise, we split into teams and tried to promote each our own superpowered microbe. (Apparently, cuteness is the best superpower, since the furry Buddy Yeast came out as the winner.)

And, dulcis in fundo, on the last afternoon we crossed the German border – and a sea of sheep – riding the fietstrein!

New review on spatiotemporal coupling of gene expression published

We combined our expertise in Gene expression regulation, Single-molecule RNA imaging, and Prokaryotic quantitative cell physiology to write a truly multidisciplinary review. It’s the product of a team effort by Alan Gerber (Amsterdam UMC), Sander van Otterdijk (Sysbio),  Frank Bruggeman (Sysbio) and Evelina Tutucci (Sysbio).

We discussed state-of-the-art imaging approaches for the measurement and quantitative understanding of gene expression, starting from the early visualizations of single genes by electron microscopy to current fluorescence-based approaches in single cells, including live-cell RNA-imaging approaches to FISH-based spatial transcriptomics across model organisms. We also highlighted how these methods have shaped our understanding of the spatiotemporal coupling between transcription and translation in prokaryotes and the future challenges in the field.

We had a lot of fun preparing some nice figures too, which illustrate our growing interest in the spatial control of gene expression across kingdoms of life.

The review “Understanding spatiotemporal coupling of gene expression using single molecule RNA imaging technologies” is now published in Transcription (https://doi.org/10.1080/21541264.2023.2199669)

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Dr. Pranas Grigaitis

Pranas successfully defended his PhD thesis, titled “Constrain and conquer: explaining metabolic strategies of microbial life through optimal resource allocation” on March 20 2023. The promotors were Bas Teusink (VU Amsterdam) and Ursula Kummer (Heidelberg); Frank Bruggeman, Jack Pronk, Maria Suarez Diez, Peter Swain, and Meike Wortel were in the thesis committee. Pranas will stay on as a Postdoc to study metabolic division of labor in ant colonies – stay tuned!

Congrats, Dr. Grigaitis!