Professor Maartje Bastings, from the School of Engineering, was awarded the prestigious European Research Council (ERC) Starting Grant.
Maartje Bastings, head of the Programmable Biomaterials Laboratory at the Institute for Materials, received a grant for her project entitled "InActioN: Intracellular Action of DNA-based Nanomaterials". This grant of 1.5 million euros, spread over five years, encourages investigator-driven frontier research in Europe through competitive funding across all fields, on the basis of scientific excellence.
“Thanks to this fund, my team and I will be able to explore the geometry of nanomaterials as sole parameter to organize cellular immunological checkpoints into an active or inhibitive state. This represents an unprecedented advance in scientific research," explains the professor.
Based on a geometric rearrangement of identical building blocks, her team will aim to provoke immune activation or inhibition exclusively by variation in spatial organization of proteins. The same material can thus be agonist and antagonist depending on the organization of molecular components. Hereby, researchers demonstrate that a precise control over geometry can define the potency of immunomodulating materials, pioneering geometry-based immune-engineering.
Scientific Abstract: InActioN: Intracellular Action of DNA-based Nanomaterials
Self-organization of matter into structured architectures with emerging functionality is arguably the most important phenomenon to enable life. Unfortunately, human efforts to successfully engineer materials that control hierarchical order and achieve precise action in cells, have suffered from structural heterogeneity and limitations in functional precision. Immune pathways are prime examples of cascades where a finely balanced sequence of interactions decides between life-changing outcomes, varying from tolerance to active fight. Immune-modulating materials, therefore, would uniquely benefit from precision control over functionality. DNA-based nanomaterials have the potential to change our current bioengineering standards due to their inherent architectural uniformity and nanometer control of functionalization, allowing for a quantitative analysis of material parameters on cell activation.
The goal of this ERC proposal is to use structural geometry of DNA-based materials to provoke controlled intracellular manipulation of immune signaling via the hierarchical and spatial organization of constitutive DNA binding proteins. We create a circular paradox where DNA defines protein synthesis, yet protein function is controlled by self-organization following interaction with designer DNA. Our approach stands out in its controlled-by-nature strategy: 1) we exclusively use materials derived from cellular building blocks; that 2) respond to stimuli generated without artificial intervention, 3) that we quantify using pathway specific activation markers and 4) image via label-free microscopy to track inherent structural changes in physical material properties. We apply our approach on two important signaling pathways involved in immunology: TLR9 as Th1 trigger for vaccine adjuvants and innate cGAS inhibition to fight autoimmunity. Using spatial organization as foundation for geometry-based immune-engineering will revolutionize the design of novel immune-modulating materials.
