ERC FUNDED PROJECTS

Aphids are devastating insect pests of crops globally, and pose a major threat to food security. Crucially, there is a lack of durable genetic crop resistance against aphids, and current control relies almost exclusively on insecticides, which are costly and damaging to the environment and to which aphids develop resistance. These insects deliver proteins inside host plants, called effectors, to suppress the plant immune system and enhance susceptibility. I recently discovered that these effectors exhibit their activity via interacting with host plant proteins pointing to important conceptual parallels between plant-insect and plant-microbe interactions. This raises important new questions that urgently need to be addressed to enable development of novel protection strategies against aphids that are durable and sustainable. These are: What is the mechanistic and structural basis of aphid effector-triggered susceptibility? How can we interfere with aphid effector-triggered susceptibility? APHIDTRAP will address these questions using an innovative strategy: 1) I will introduce a structural biology approach to the insect effector biology field to reveal protein 3D structures of aphid effectors and their host protein targets in bound and unbound state, and determine how mutations in these proteins affect interactions and protein functions. 2) I will use both natural variants and mutants of effectors and host protein targets, combined with in planta functional assays to explore plant-aphid molecular co-evolution. 3) I will identify host protein target interactomes and investigate how mutations affect network functionality. 4) I will use information generated in 1-3 to develop and apply a synthetic biology approach to prevent aphid effector-triggered susceptibility in potato crop plants. APHIDTRAP’s vision is to elucidate the mechanisms that underlie susceptibility to aphids and investigate how we can interfere with these to reduce crop susceptibility to insect pests.

1 999 992 €

Start date: 2021-06-01, End date: 2026-05-31

Spider silk is Nature’s high performance material that has the potential to revolutionize the materials industry. However, production and spinning of artificial spider silk fibers are challenging, and current methods to produce silk fibers include denaturing conditions which prevent the silk proteins from assembling into fibers in the same complex way as native silk proteins do. In order to fulfill the potential of spider silk we need to increase our understanding of the silk formation process and decipher how protein folding and interactions relate to mechanical properties of the resulting silk fiber. Recent insights into the physiology and molecular mechanisms of the spinning process has made it possible to develop a biomimetic artificial spider silk spinning device (see our publications Andersson et al. Nat Chem Biol. 2017; Otikovs et al. Angew Chemie Int Engl Ed. 2017). We are, for the first time, able to spin artificial silk fibers in which the proteins adopt correct secondary, tertiary and quaternary structures. The overall objective of ARTSILK is to build on these recent technical leaps and use state-of-the-art technologies to generate artificial silk fibers that are equal or superior to native spider silk in terms of toughness and tensile strength. To reach the overall objective we will use the recently mapped spider genome, protein engineering and single cell RNA (ScRNA) sequencing to design novel silk proteins for fiber production. We will also study the relationship between protein secondary structure formation and fiber mechanical properties in order to decipher the ques that determine mechanical properties of the fiber. This knowledge will be important also for the basic understanding of how soluble proteins covert into b-sheet rich fibrils in, e.g., Alzheimer’s disease. Finally, we will use microfluidic chips to engineer the next generation spinning device and 3D-printing techniques to make reproducible three-dimensional structures of spider silk.

2 000 000 €

Start date: 2019-05-01, End date: 2024-04-30

Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors. The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.

1 977 781 €

Start date: 2015-09-01, End date: 2020-12-31

As nature’s first bioengineers, bacteriophages have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tools. Thus, BIONICbacteria will provide conceptual novel synthetic biology tools that allow direct manipulation of specific protein activity, post-translational modifications, RNA stability, and metabolite concentrations. The goal of BIONICbacteria is to pioneer an unconventional way to perform synthetic biology, tapping an unlimited source of novel phage tools genetic circuits and phage modulators. To achieve these goals, we will apply and develop state-of-the-art technologies in molecular microbiology and focus on three principal aims: (1) To exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis. (2) To build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner. (3) To create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations and vaccine design. This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to domesticate Pseudomonas strains in radically new ways. By building proofs-of-concept for applications in industrial fermentations and vaccine development, we address key problem in these areas with potentially high-gain solutions for society and industry.

1 998 750 €

Start date: 2019-09-01, End date: 2024-08-31