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New unique imaging facility at DTU

Friday 08 Jan 21

Contact

Lone Gram
Professor
DTU Bioengineering
+45 45 25 25 86

Contact

Aaron John Christian Andersen
Metabolomics Core Manager
DTU Bioengineering
+45 45 25 61 38

New instruments in the platform

  • Upgrade of a confocal microscope (Leica SP8)
  • A four- laser fluorescence assisted cell sorter (Sony MA900)
  • A cell counter (Miltenyi MACSQuant VYB)
  • A luminescence microscope (Nikon Ti2)
  • A MALDI QTOF MSI (Bruker TIMS-ToF Flex)

MALDI MSI

The instrument is a Bruker TIMS-TOF Flex, and the most important feature of the instrument is that it is able to perform mass spectrometry imaging (MSI), revealing the location of metabolites on two-dimensional surfaces. It is also capable of the trapped ion mobility separation (TIMS), which brings another dimension of separation to LC-MS and MALDI-MS experiments. TIMS is able to separate ions (charged molecules) based on their cross-sectional area, a method which complements chromatographic or spatial separations resulting in much richer metabolomic datasets.

The facility is a major step on the road to targeted use of microbiomes for biological control of disease-causing organisms.

13,7 M DKK from the Novo Nordisk Foundation has enabled the Center for Microbial Secondary Metabolites (CeMiSt) and DTU Bioengineering to establish a research facility which will be an unprecedented tool in the work on microbiomes, the interactions between microorganisms and the application of this understanding in plant biocontrol, aquaculture probiotics, human probiotics and the fight against antimicrobial resistance.

The rapid development and spread of antimicrobial resistance, rated by the WHO as one of the major threats to humanity, makes the development of novel disease control strategies urgent.

Directing or engineering the microbiome, the mixed-species community of microorganisms associated with a host or a niche, has emerged as one of the most promising avenues for a sustainable bio-based control of pathogens.

Several studies in humans, animals and plants have shown that adding particular living microorganisms or microbial extracts or compounds may offer disease protection - sometimes. However, the molecular mechanisms underlying successful trials – or explaining the unsuccessful trials – are in most cases unknown. How is the molecular (chemical) interactions between microorganisms and between microorganisms and host?

The new facility is aimed at answering these questions. It is a unique imaging facility that combines high-resolution optical imaging systems for live microbial cell imaging with forefront analytical technologies that enable spatial visualization, identification, and quantification of the chemical compounds and molecules in situ (in the natural environment) in biological samples.

Professor and Center Leader of CeMiSt Lone Gram that together with several colleagues have received funding for the new facility adds:

“To unravel the chemical signaling inside complex communities, e.g. in biocontrol synergistic organismal relationships, we need to determine which signals are sent, by which organism and where. Using the facility, we can identify the nature of the signals, and by overlaying these chemical maps onto high resolution imaging, we can pin-point the actors and their roles in this signaling network in situ.” 

MALDI photo

Figure: A mass spectrometry image (MSI) of Phaeobacter inhibens colonies taken by a Bruker TIMS-TOF Flex. Phaeobacter inhibens is a marine bacteria and is known to produce small secondary metabolites with powerful bioactive properties. In this image we can see the distribution of these molecules and from this distribution we can infer that the metabolites are primarily located within the colonies, and more so at the outer edge of the colonies. Typically with MSI it can be difficult to image such small metabolites, but the Bruker TIMS-TOF Flex manages to do so with far greater mass resolution, and much greater sensitivity than our current instrumentation. Each pixel in this image is 40 µm.

The imaging facility will enable the study of complex microbial chemical ecology in natural and engineered microbiomes, determine the conditions and identify effector molecules associated with for instance disease suppressive conditions. Also, it will allow the determination of where and how, in physical space, a microorganism (or a population) must be situated to exert an effect. This, in turn, will enable a more directed selection and engineering of microbial strains as well as a strategy for their actual physical application.

The imaging facility will be part of the DTU Metabolomics Core headed by Aaron Andersen, and the DTU Bioimaging Core headed by Claus Sternberg. Services will be available to academic and industrial partners.

 

Udefra med kran Forskerne inspicerer MALDI

Photo text: The MALDI MSI is one of the most important instruments in the new facility and is the first of its type to be installed in Scandinavia. Here it is lifted into its place at DTU and following that thoroughly inspected. Photo: Charlotte Gotfredsen

https://www.food.dtu.dk/english/news/nyhed?id=%7B5E67A4F7-9104-45E6-95DB-786FA06C7A52%7D
17 APRIL 2021