Introducing single cell analyses in microbiology by unifying next generation FACS and sequence analysis

Name of applicant

Søren Johannes Sørensen

Title

Professor

Institution

University of Copenhagen

Amount

DKK 5,754,000

Year

2022

Type of grant

Research Infrastructure

What?

This project will provide a FACSymphony Sorter S6 for integration into an existing research facility at the University of Copenhagen to create a platform enabling genetic investigation of individual bacteria cells in complex populations or communities. The FACSymphony Sorter S6 can sort individual bacteria with specific characteristics from a population based on their phenotype. For example, using fluorescent labeled probes to isolate single bacterial cells with specific antibiotic resistance traits. When integrated into the existing infrastructure pipeline at the University of Copenhagen the entire genomes, and/or the expressed genes of all the sorted cells can then be sequenced uncovering the mechanisms behind the observed antibiotic resistance. This project will create the first microbial single cell sequencing center in Denmark - SinSeq.

Why?

Genomic and metagenomic characterizations of bacteria are traditionally performed on populations of millions of cells. However, bacteria of the same species can be vastly different, just as humans are vastly different. Therefore, some questions can not be answered by investigating the average of a large population, but must be answered by investigating the individual bacterial cell. Studying microorganisms at the single cell level is difficult and expensive, requiring facilities that are unobtainable for most researchers. Therefore, this project will combine existing infrastructure with a state-of-the-art cell sorter making for the first time such facilities available to academic and industrial researchers in Denmark. Specifically, we will use this facility to advance our knowledge of how antibiotic resistance genes are exchanged between different species of bacteria, a current knowledge gap that has accelerated the current antibiotic resistance crisis where bacterial infections are difficult to treat with antibiotics. We will investigate the spread of antibiotic resistance genes across complex microbial communities from clinically relevant environments such as the human gut to identify novel strategies to stop resistant organisms from spreading. We will also use the technology to identify novel beneficial organisms that can prevent infections and probiotic bacteria that help us stay healthy or make sure that useful bacteria do their job using less chemicals or energy when making biodiesel or producing food keeping agro- and biotech industry sustainable under changing climatic conditions.

How?

The facility will initially be available to a wide range of local users in the Greater Copenhagen region, many of whom wish to mention their support. These include partners from emerging technology, the established industry, and the research community such as: Snipr Biome’s Jakob Haaber, Clinical Microbiomics’ Henrik Bjørn Nielsen, Riverstone Biotech’s Katrine Bych Kampmann and Scifeon’s Martin A. Hansen. Chr Hansen’s Adam Baker and Novozymes’s Ana Filipa da Silva. Leaders of Danish Centers of Excellence: Lone Gram (DTU), Tom Gilbert (KU Globe) and Riikka Rinnan (KU, BIO). A wide range of disciplines in the research community in general represented by Karen Krogfelt (Roskilde Uni.), Dan Stærk (KU, SUND), Lars H. Hansen (KU, PLEN), Dennis Nielsen (KU, FOOD), colleagues from other sections at KU BIO: Karsten Kristiansen, Morten Petersen, Michael Poulsen, Jakob Winter and many more. The user group will expand once the facility is running. Then the users will simply send a sample of a living microbial community that will then be integrated into a flexible project pipeline enabling rapid investigation for a broad range of disciplines. Users will only pay incurred costs, enabling accessibility while ensuring expert technicians, service contracts and consumables will be covered for the expected project lifetime (10-12 years).

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