We work at the interface of microbial genomics, ecology, and functional genetics to understand, engineer, and control bacterial systems that relate to medicine, sustainable agriculture, and biotechnology. Our work is largely centered on Pseudomonas species that are either devastating pathogens themselves (such as the human ESKAPE pathogen Pseudomonas aeruginosa), or Pseudomonas species that inhibit growth of other pathogens (such as Pseudomonas protegens that inhibit soil borne plant pathogens and may work as biological control agents in agricultural settings). We work mainly with natural isolates (which we sample from human, plant or soil ecosystems) rather than domesticated laboratory strains, and base our engineering and control efforts on mechanistic insight.
Our research activities are within these interconnected areas:
1. Ecology and engineering of microbial communities
Our goals in this area are centered on developing microbial-based therapeutics for maintaining beneficial microbial communities and defeating microbial pathogens in connection to plant and human diseases.
Whether in the human host or in soil, pathogens are interacting with other co-existing microbial species, and such interactions may either limit pathogen colonization or potentiate pathogen expansion and virulence. This point toward an exciting area for novel treatment/control strategies based on biological interference with microbial interaction networks or direct inhibition of the pathogen. Within this area we work to determine the molecular basis of microbe-microbe interactions and how these interactions modify pathogen physiology, virulence and resistance, we investigate how community interactions are modified by evolution and vice versa, and isolate biocontrol strains and/or construct bacteria with pathogen-inhibitory activities. We are also aiming at determining how microbial cells and their activities are spatially distributed within microbial biofilm communities and in complex natural environments.
2. Unraveling the role of microbial secondary metabolites in natural microbial systems
The lab is part of the Center of Excellence, Center for Microbial Secondary Metabolites, CeMiSt, which is led by Professor Lone Gram. Our activities in CeMiSt revolves around understanding the role of the genetic and chemical diversity of Pseudomonas species in soils. We are currently developing/applying synthetic biology tools to be able to manipulate secondary metabolite production in different Pseudomonas species, and work with chemists to detect and quantify these molecules.
3. Engineering and evolution of bacterial regulatory networks
Our goals in this area are centered around understanding and predicting bacterial evolution in response to perturbation of human and soil associated microbial communities.
Bacterial regulatory networks are frequent targets of evolution in response to ecosystem changes. Understanding, predicting, and eventually controlling such network modifications is important in relation to e.g. optimal performance of biocontrol strains in the environment, and minimizing antibiotic resistance development in pathogens. Our efforts are currently focused on determining the ‘ground-rules´ of how regulatory networks are being shaped by evolution, how genetic changes in either transcription factors or cis-regulatory elements impact their function at the molecular level, and in which way regulatory evolution changes important cellular phenotypes (such as resistance towards toxic inhibitors (e.g. antibiotics), biofilm formation, virulence, and bioactivity/interaction with other microbes).
4. Translational microbiology and antibiotic resistance evolution
Our work in this area is broadly aimed at providing better guidance for clinicians in relation to sequence-based diagnostics, treatment, and prevention, and to identify novel target for interference and/or biomarkers.
We use sequencing and functional genomics to define population structures of pathogens, unravel their transmission networks, and determine pathogen evolution during adaptation to host/microbiome environments. A particular focus is on determining the genetic causes of antibiotic resistance development in human pathogens in response to drug therapies. An important element of our activities is to use sequence information as a starting point to establish direct links between the genome sequence and the physiology and behavior of the microbe. Such genotype/phenotype relationships allow us to identify novel (and often unexpected) mutational pathways underlying antibiotic resistance and/or virulence evolution. Our focus is currently on Pseudomonas aeruginosa (one of the major ESKAPE pathogens) and Mycobacterium tuberculosis (perhaps the world’s most successful pathogen).