The blood-brain barrier is a sophisticated biological barrier comprising several different cell types, structured in a well-defined order with the task to strictly control the passage of molecules - such as drugs against neurodegenerative diseases - from the blood into the brain. To reduce the ethical and economic costs of drug development, which in EU today uses ~10 million experimental animals every year, we must develop in vitro models of the blood-brain barrier with high in vivo correlation, as these are completely missing today. SONGBIRD aims to achieve this with the scientific approach to - Develop advanced microfabrication methods to handle biologically derived materials - Structure the materials into heterogeneous 3D multi-layer suspended cell culture scaffolds - Incorporate blood-brain barrier cells with precise control on location and order - Integrated the 3D scaffolds into a microfluidic network as a miniaturised screening platform The vision is to develop and validate versatile microfabrication methods to mechanically structure and physically handle soft biological materials to unlock the use of next generation animal-free barrier-on-chip models that can be used to speed up drug development, serve as screening platforms for nanotoxicology and help medical researchers to gain mechanistic insight in drug delivery. During SONGBIRD, I will focus on the blood-brain barrier due to its urgent relevance for drug development for the ageing population but the final processing tool-box will be suitable for realising in vitro models of any biological barrier in the future. SONGBIRD is proposed to run for 60 months and will include researchers with expertise in microsystem engineering (PI), hydrogel synthesis and drug delivery. The expected output is a validated 3D barrier-on-chip model as well as a microfabrication toolbox for biological materials enabling transformation from 2D to 3D cell cultures in several other life science research areas.

The main hypothesis of the proposed research is that, contrary to common and long-standing belief, mitochondrial genetic variation is functional and plays a key role in evolutionary adaptation. I suggest that a novel understanding of selection on mtDNA can derive from simultaneously considering sex-specific selection and genetic interactions between mtDNA and nDNA. Because males are a genetic “dead-end” for mtDNA, mtDNA mutations that are detrimental for males but beneficial for females will spread. This will generate a male-specific genetic load (“the mother’s curse”). Further, the main energy producing pathway in eukaryotes (the OXPHOS pathway) is built collectively by products of the mitochondrial and the nuclear genome. Thus, mtDNA and nDNA are potentially entangled in an intricate web of epistatic interactions that dictates organismal metabolism. The proposed research is built upon a series of interrelated parts, and will use a very amenable insect model organism and employ a range of different research methodologies. Specific aims of the proposed research is (1) to assess the effects of mito-nuclear genotype on key life history traits such as metabolic rate and test whether these effects are sex-specific in line with the “mother’s curse” and (2) to test the hypothesis that mito-nuclear interactions promotes the maintenance of polymorphism in mitochondrial genome through negative frequency dependent selection. This research will have a range of biological implications, ranging from applied medical genetics over our use of mitochondrial genetic markers in population genetics/biology to speciation and our understanding of thermal adaptation to climate change.

Can spin integrated circuits (Spin-ICs) with low power-high speed processing capabilities be realized? What are the key ingredients necessary to catapult present-day spintronics to make such a leap? The emergence of two-dimensional (2D) quantum crystals provides new impetus for exploring ambitious ultralow-power and ultrafast speed prospects of spintronics and nanomagnetism. Atomically thin 2D quantum materials like graphene have created novel possibilities for pure spin current communication, functionalities, and controlling spin phenomena, for inventing entirely new kind of spin components, that could pave the way for spin ICs. SPINNER aims to unleash these prospects leveraging the PI’s pioneering leadership and recent innovations in flexible graphene spin circuits, breakthrough longest spin communication in graphene, and precision characterization of 2D magnetic crystals, aiming for three highly ambitious objectives: (1) Achieving strain control of spin currents and spin Hamiltonian in 2D materials. (2) Enabling field-free pure spin current torque functionalities in graphene spin circuits. (3) Controlling ultrafast spin currents at 2D spinterfaces. The proposed new experiments in SPINNER build upon the PI’s expertise in state-of-the-art spin and charge transport, µ-Hall magnetometry, advanced nanofabrication, and device engineering, augmented with new strengths in magneto-optic Kerr effect and ultrafast spin dynamics experiments. Designed for unprecedented engineering of spin materials and devices, the success of SPINNER will reveal new performance, low-power spin functions, determining the ultimate efficiency and speed of pure spin-current operations for Spin-ICs, leading to multiple new scientific and technological breakthroughs. Realizing SPINNER will make a significant impact on 2D quantum materials, flexible nanoelectronics, nanomagnetism and spintronics, and device physics, proving its high multidisciplinary worth.