ERC FUNDED PROJECTS

Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.

1 422 339 €

Start date: 2016-07-01, End date: 2021-06-30

Space benefits mankind through the services it provides to Earth. Future space activities progress thanks to space transfer and are safeguarded by space situation awareness. Natural orbit perturbations are responsible for the trajectory divergence from the nominal two-body problem, increasing the requirements for orbit control; whereas, in space situation awareness, they influence the orbit evolution of space debris that could cause hazard to operational spacecraft and near Earth objects that may intersect the Earth. However, this project proposes to leverage the dynamics of natural orbit perturbations to significantly reduce current extreme high mission cost and create new opportunities for space exploration and exploitation. The COMPASS project will bridge over the disciplines of orbital dynamics, dynamical systems theory, optimisation and space mission design by developing novel techniques for orbit manoeuvring by “surfing” through orbit perturbations. The use of semi-analytical techniques and tools of dynamical systems theory will lay the foundation for a new understanding of the dynamics of orbit perturbations. We will develop an optimiser that progressively explores the phase space and, though spacecraft parameters and propulsion manoeuvres, governs the effect of perturbations to reach the desired orbit. It is the ambition of COMPASS to radically change the current space mission design philosophy: from counteracting disturbances, to exploiting natural and artificial perturbations. COMPASS will benefit from the extensive international network of the PI, including the ESA, NASA, JAXA, CNES, and the UK space agency. Indeed, the proposed idea of optimal navigation through orbit perturbations will address various major engineering challenges in space situation awareness, for application to space debris evolution and mitigation, missions to asteroids for their detection, exploration and deflection, and in space transfers, for perturbation-enhanced trajectory design.

1 499 021 €

Start date: 2016-08-01, End date: 2021-07-31

Microswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing. However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale. This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers. To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.

1 497 500 €

Start date: 2016-09-01, End date: 2021-08-31

My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014. The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized. Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.

1 525 000 €

Start date: 2016-03-01, End date: 2021-02-28