SARS-CoV-2 has revealed serious inadequacies in how we track infectious disease spread. Despite progress in quantifying individual-level biomarkers at scale, inferring transmission dynamics to inform public health decisions still largely depends on counting cases. Recently, I showed that individual-level viral load measurements from a single cross-sectional sample of RT-qPCR data can accurately estimate an epidemic’s trajectory, overcoming many limitations of case count-based surveillance. Here, I will build a new generation of outbreak analytic tools, leveraging individual-level immunological and pathogen titres to robustly estimate transmission dynamics. First, I will integrate virologic and serologic data from the UK’s SARS-CoV-2 surveillance studies to create a new modelling framework coupling within-host viral and antibody kinetics with population-level dynamics. Using this framework, I will evaluate prioritization of different surveillance strategies across pandemic phases. Second, I will develop new epidemiological inference methods harnessing biological kinetics, validated using UK SARS-CoV-2 data, and evaluated for use in resource-limited settings. Finally, I will integrate viral load data with phylodynamics to improve the rapid characterization of emerging viral variants. Overall, this research will advance how we use individual-based information for infectious disease surveillance, establishing the study of viral load dynamics, or viroepidemiology, as a key tool alongside seroepidemiology and phylodynamics.

The formation and maintenance of bilateral symmetry of the vertebrate body is intimately related to developmental abnormalities such as scoliosis and neural tube defects. The body axis forms in the early embryo when multiple tissues undergo drastic morphogenesis. The mechanical forces and their underlying cellular dynamics that ensure body axis symmetry are poorly understood. I hypothesize that the paraxial mesoderm produces lateral compression on the axis to prevent it from bending. To test this hypothesis, we will image cell and tissue dynamics of body axis formation in chick embryos. Using this information, we will develop biophysical models that predict tissue forces. These models also allow theoretical assessment of the constraints and key parameters that control variability of symmetry. Using surgical ablations and molecular perturbations on different body axis tissues, we will analyze the cellular and tissue mechanisms of asymmetry response and correction. Using a novel device combining high-sensitivity cantilevers coupled with position control and live imaging, we will quantify and alter both forces and mechanical properties of different tissues. Together, these approaches will integrate quantitative maps of cell dynamics, tissue shapes and soft matter mechanics that are essentially a physical solution of body symmetry formation and morphogenesis in general. How a single cell becomes a functional individual is one of life's biggest mysteries. A sophisticated structure like the eye forms from a collection of tissues during the development of an embryo. These tissues grow and deform and interact with each other to construct an organ. The mechanical forces that the tissues create and experience during this process are poorly understood. This knowledge is important as it might explain how developmental defects take place and provide guidance for engineers to create replacement organs and tissues from stem cells. This proposed project studies the particular feature of body axis symmetry, namely the formation of a straight spine, in vertebrate embryos (including human). We aim at combining imaging, theory and biomechanics to identify the forces that straighten different tissues of the body as they grow, and to find the mechanisms that correct curvatures and the situations when such mechanisms fail.