Research
Current research
Bridging environmental and synthetic microbial ecology
Microbial communities are important in health, disease, industry, and the environment. My ultimate goal is to find unifying principles in the interaction of ecology and evolution in microbial communities that can lead to a predictive understanding of community function and resilience. My work focuses mostly on environmental, especially marine, bacteria, their physiology and interactions. I am particularly interested in how trophic interactions, in which the metabolic excretions of one species are the primary resource for another, shape community assembly. Such trophic interactions are ubiquitous and drive many heterotrophic bacterial communities, as we have highlighted in a recent Perspective. I approach the study of microbial community dynamics through the lens of metabolism, on three scales: individual species, synthetic communities, and in situ mesocosms. To this end, I combine experiments (high-throughput and quantitative microbial physiology, community assembly experiments), bioinformatics (statistical analysis of large environmental datasets, comparative genomics, genotype-to-phenotype mappings) and mathematical theory (consumer-resource and other community models).
Postdoctoral research
Characterizing metabolic niches of marine copiotrophs
Since trophic interactions can only be understood if the metabolic capabilities of each interacting species are known, I began by cataloguing the metabolic capabilities of a library of 186 marine heterotrophic bacteria. These strains were isolated from polysaccharide particles incubated with seawater, and they represent many of the commonly observed particle-attached taxonomic groups in the ocean. To characterize their metabolic traits, I developed a high-throughput method to measure the growth rate of each strain in 140 different substrates, from amino acids to polysaccharides, yielding over 23000 phenotypes. Extracting statistical patterns from these phenotypes, I found that the metabolic niche of all isolates could be described to a first approximation in terms of their relative preference for sugars (i.e., glycolytic substrates) and organic and amino acids (i.e., gluconeogenic substrates). This result provides a framework for understanding metabolic niches that is rooted biochemical constraints (between glycolysis and gluconeogenesis) in central metabolism, highlighting the strength of high-throughput trait characterization approaches. Read the paper here!
Public good exploitation in natural bacterioplankton communities
Public goods exploitation can occur when microorganisms have to secrete costly molecules, such as siderophores or hydrolytic enzymes, into the environment to access nutrients. However, predicting such interactions in natural communities is difficult because assigning phenotypes to observed genotypes is complicated by missing gene annotations and the inability to validate predictions. I collaborated with a postdoctoral scholar at MIT to address this problem in the context of the degradation of organic matter. Combining coevolutionary genomics with experimental characterization of 60 marine isolates and synthetic communities assembly experiments, we uncovered a stable three-level trophic structure in chitin-degrading communities, consisting of degraders (secreting hydrolytic enzymes that degrade chitin into oligosaccharides), exploiters (consuming oligosaccharides without producing hydrolytic enzymes) and scavengers (persisting on metabolic waste products). While only degraders could grow on the primary resource, exploiters, which share many genomic features with – but are not necessarily closely related to – degraders, are abundant in natural communities and have the potential to hinder degradation. Because the functional classifications were predictable from genome content, our results may help discover similar archetypal community structures in other polysaccharide-degrading communities, including from metagenomes. The research is published here.
The impact of the viral shunt on microbial recyclers and the fate of carbon in algal blooms
Environmental bacterial communities are often not isolated but engage in constant interactions with the surrounding eukaryotic communities containing protists, phytoplankton, etc. How do these interactions between bacteria, eukaryotes, and the environment shape ecosystem function? In an international collaboration spearheaded by the Vardi lab at the Weizmann Institute in Israel, I addressed this question in the context of an induced bloom of the cosmopolitan coccolithophore E. huxleyi in replicate in situ mesocosms. By analyzing a large dataset of the major biological and biogeochemical players, I studied - in a joint effort with Flora Vincent from the Vardi group (now at EMBL) - the effects of viral infection on algal bloom. Viral infection had a big influence on the whole ecosystem: We found changes extracellular carbon release, the succession of the accompanying bacterial and eukaryotic microbiomes, shifts the balance between prokaryotic and eukaryotic organic matter recyclers in algal blooms. Published here.
Doctoral research
The role of environmental heterogeneity in microbial range expansions
The population genetics of most range expansions is thought to be shaped by the competition between Darwinian selection and random genetic drift at the range margins. These range margins can be shaped by environmental heterogeneities, such as mountain ranges, rivers, or other kinds of habitat fragmentation. Tracking mutant clones with a tunable fitness effect in bacterial colonies grown on randomly patterned surfaces we show that the evolutionary dynamics during range expansions is highly sensitive to additional fluctuations induced by these environmental heterogeneities. The effect is most dramatic in mutations altering fitness, which can have nearly neutral dynamics in highly fragmented environments. Time-lapse microscopy and computer simulations suggest that this effect arises generically from a local ’pinning’ of the expansion front, whereby stretches of the front are slowed down on a length scale that depends on the structure of the environmental heterogeneity. This pinning focuses the range expansion into a small number of ’lucky’ individuals with access to expansion paths, altering the neutral evolutionary dynamics and increasing the importance of chance relative to selection.
Neutral diversity in colonies from spontaneous mutations
The genetic diversity of growing cellular populations, such as biofilms, solid tumors, or developing embryos is thought to be dominated by rare, exceptionally large mutant clones. We tracked large mutational clones (“jackpot events”) in microbial populations using fluorescent microscopy and population sequencing. High-frequency mutations were massively enriched in microbial colonies compared to well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. We provide a mathematical theory that explains the observed excess of jackpot events and predicts their role in promoting rare evolutionary outcomes. In particular, we show that resistant clones generated by surfing can become unleashed under high selection pressures and thus represent a drug resistance hazard for high-dose drug treatments. An excess of mutational jackpot events is shown to be a general consequence of non-uniform growth and, therefore, could be relevant to the mutational load of developing biofilm communities, solid tumors and multi-cellular organisms.
Video: time lapse movie over 74 hours of a colony of budding yeast grown from a single cell. This strain of yeast is engineered to stochastically switch color from expression of RFP (false colored magenta) to GFP (false colored yellow) at a fixed rate of about 1/1000 cell divisions.
ncomms12760-s2.movAdaptation from standing variation
The coupling of ecology and evolution during range expansions enables mutations to establish at expanding range margins and reach high frequencies. This phenomenon, called allele surfing, is thought to have caused revolutions in the gene pool of many species, most evidently in microbial communities. It has remained unclear, however, under which conditions allele surfing promotes or hinders adaptation. Here, using microbial experiments and simulations, we showed that, starting with standing adaptive variation, range expansions generate a larger increase in mean fitness than spatially uniform population expansions. The adaptation gain results from ‘soft’ selective sweeps (the sectors seen in the video above) emerging from surfing beneficial mutations. The rate of these surfing events sensitively depends on the strength of genetic drift, which varies among strains and environmental conditions (see video below).
Video: tracing cell lineages in single-cell scale time lapse movies shows that the local dynamics differs strongly between species (budding yeast on the left, E. coli on the right), impacting the strength of genetic drift in microbial colonies.
lineages-both.mp4Effects of flow on resistance evolution in antibiotic gradients
Antibiotic gradients can increase the rate of resistance evolution because spontaneous resistance mutations arising in regions of intermediate antibiotic concentration have a large advantage over their local competition, allowing them to take over the population and expand freely into unoccupied territory (where the concentration is too high for susceptible individuals to survive). Extending previous works by Greulich et al. and Hermsen et al., who modeled adaptation on antibiotic gradients without convection, we examined how convection can shape the adaptation dynamics on gradients using a mathematical framework based on branching random walks and identified the relevant length and flow speed scales.
Figure: the rate of adaptation (i.e., the rate of emergence of resistance) in antibiotic gradients as a function of gradient steepness (λ /l) and convection speed. Flow towards higher antibiotic concentrations speeds up resistance evolution.
