Seven innovative Villum Experiment grants to the Department of Biology!

- “It is truly a spectacular result underlining BIO as one of the strongest research environments within the natural sciences in Denmark” says Head of Department, Niels Kroer.

The seven elected research projects from BIO spans from Solving the Carbon Paradox in Marine Plants, over Tailoring yeast for human membrane protein structural biology, to Surveillance of microbial small talk using Trojan horses.

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Jonas Stenløkke Madsen, Assistant Professor (tenure track) 

Project: BioRep-HGT: Bio-reporting horizontal gene transfer. An experimental tool that eliminates selection-dependency

Grant: DKK 1.7 million

Bacteria are extremely good at adapting to many different environments; they can infect humans and even survive antibiotic treatment by becoming resistant. A unique way in which bacteria adapt is by transferring genes for new traits, such as those encoding for antibiotic resistance. In the BioRep-HGT project, we will develop new molecular techniques to study such gene transfer. Our goal is to make so-called bioreporters, in which bacteria emit fluorescent light when acquiring new genes. By doing single-cell transcriptomics, we will identify genes that are expressed only when gene transfer occurs. The promoters of these candidate genes will then be fused to GFP to construct the bioreporters. With these bioreporters, we will be able to unravel fundamental aspects of gene transfer.

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Kasper Elgetti Brodersen, Postdoc

Project: Solving the Carbon Paradox in Marine Plants

Grant: DKK 2 million

I will investigate whether localized micro-acid zones on leaves enhance the photosynthetic carbon fixation in seagrass plants. A novel experimental approach for mapping pH microenvironments will be developed utilizing pH sensitive optical sensor nanoparticles incorporated into an agar matrix that is deposited on seagrass leaves and imaged with a camera system. The project will for the first time map the distribution and dynamics of micro-acid zones on the leaf surface and how such zones can stimulate CO₂ formation within the leaf diffusive boundary layers of marine plants. That is, via increased dehydration of HCO₃^- to CO₂ by extracellular carbonic anhydrase activity, as well as, via simple low pH-driven changes in the carbonate speciation towards CO₂.

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Lars Båstrup-Spohr, Assistant Professor

Project: Plain of Jars – the world’s oldest man-made biological experiment

Grant: DKK 1.9 million

Biotic communities, which can be found the most extraordinary places, are assemblages of species that interact at a given location. The environment and isolation influence communities by selecting for species with the right characteristics, or traits, enabling them to reach and thrive in a given ecosystem.

Scattered across the landscape in central Laos, thousands of large stone jars have been left from ancient burial rituals. Together, these jars form a massive biological experiment: for 2000 years, rainwater has interacted with geology to create unique yet perfectly replicated ecosystems that include organisms ranging from microbes to aquatic plants. The unprecedented age and high number of virtually identical replicates offers a unique opportunity for unfolding one of ecology’s long-standing questions: What shapes biological communities? Using novel sampling techniques, the project will strengthen the understanding of the importance of environmental conditions and habitat isolation for biodiversity in aquatic ecosystems.

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Martin Willemoës, Associate Professor

Project: PCOG-Precursors for inserting complex O-linked glycans into synthetic glycopetides

Grant: DKK 1.6 million

Are orally or intravenously administered peptide drugs more potent/stable if modified with human O-linked glycans? Complex glycosylation constitutes a limitation in the completion of synthetic peptides and recombinant proteins for pharma and research. Peptide glycosylation is either achieved through low yield, multistep chemical synthesis or alternatively through production organisms or cell-cultures either performing non-native glycosylations or adding correct glycans but at a small scale and with high expenses. The project delivers an enzyme-based platform utilizing preformed O-glycans from bulk, cheap O-glycosylated proteins such as mucins. The project will focus on synthesis of anti microbial peptides with a correct composition and structural integrity of human O-glycosylation stabilize such peptides when passing through the stomach and intestine or injected into the blood.

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Per Amstrup Pedersen, Professor MSO

Project: Tailoring yeast for human membrane protein structural biology; humanizing yeast membrane lipid composition

Grant: DKK 1.7 million

Controlled exchange of matter and information between a cell’s interior and exterior is performed exclusively by chemically selective membrane spanning proteins. Understanding membrane protein structure is therefore vital for comprehending human physiology. It is therefore a huge challenge that essentially all human membrane proteins cannot be purified from native tissue and are challenging to produce and purify. We have successfully developed a yeast expression platform for human membrane protein production resulting in a number of high-resolution membrane protein structures. However, the lipid environment experienced by a human membrane protein produced in yeast deviates significantly from that present in the native human cell. This counts for phospholipid fatty acid chain length, the degree of fatty acid unsaturation and steroid composition. To deposit recombinant human membrane proteins in a more native like membrane environment we will attempt to engineer our yeast expression system to produce membranes resembling those found in humans.

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Urvish Trivedi, Postdoc

Project: Surveillance of microbial small talk using Trojan horses

Grant: DKK 1.8 million

Bacteria communicate with one another using chemical signaling molecules as words. They release, detect, and respond to the accumulation of these molecules through a process called quorum sensing. This project aims to engineer and characterize novel synthetic “Trojan horses” that can target bacteria based on species-specific communication signals. This proof of concept will address key questions including how to intercept communication signals made by target bacteria to deliver target-specific toxins, and how to activate and control such a system with high specificity using inducible promoters. This experiment can open a brand-new avenue and cause a paradigm shift in favor of using synthetic biology as part of future antimicrobial strategies.

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Karsten Kristiansen, Professor

Project: The origin of the vertebrate brain

Grant: DKK 2 million

In this project, we will study the origin and evolution of the vertebrate brain and spinal cord. Brain or brain-like structures are found widespread in the animal kingdom, but brains are not identical, i.e. the brains found in animals like the nematode, fruit fly, or earthworm are fundamentally different from the vertebrate brain.  Our hypothesis is that the vertebrate brain is a unique structure, and that major genomic rearrangements putting “old” genes into a new context were the prerequisite for this development. During evolution of vertebrates from their invertebrate ancestors, the nervous system seems to have gone through a set of major specialisations from a larval brain, mainly innervating ciliary bands (as seen in echinoderms and enteropneusts), via a simple neural tube (as seen in Amphioxus) to a system having a neural tube and a well-developed brain as found in cyclostomes at the base of the vertebrate tree. By combining anatomical (in this case in situ expression of neural genes) and genomic data (in this case whole genome sequencing of selected animals), we want to uncover if internal shifts in position of genes already present in our invertebrate ancestors (and chromosome/gene duplications known to have occurred early in the vertebrate history) can explain the stepwise evolution of the vertebrate brain. The project aims to achieve a much better understanding of how anatomical characters can change rapidly, without major changes in individual genes, due to changes in gene environment and topography of the genes coding for anatomical characters.

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