Adaptive immune responses to challenges such as infections and vaccines are initiated and executed by the actions and interactions of single cells. The ultimate outcome of an immune response is determined by many factors, but most important are (1) the antigen specificity conferred by variable lymphocyte antigen receptors, and (2) the effector functions of the responding lymphocytes. In this project I propose to develop a method to study these two factors simultaneously at complete receptor (both subunits) and single-cell resolution. I will apply this new method to gain unprecedented insights in the adaptive immune system at steady-state and upon immunization. I will perform this work as a postdoctoral fellow at The Rockefeller University (New York, US) in the Rosenberg laboratory, where bioinformatics and cutting-edge high-throughput techniques are developed to essay the immune system.

Hearing loss has second highest prevalence of disabilities worldwide. Many cases involve cochlear damage and, more specifically, damage to the outer hair cells. In search of protection and possible restoration of normal hearing it is imperative to know the exact function of these cells. Under normal conditions outer hair cells exert force within the organ of Corti, leading to frequency selectivity and adaptation to sound intensity. This involves two mechanisms: hair cells can actively move their hair bundle; and length of an outer hair cells body can change. However, these findings come from preparations of isolated or dissociated outer hair cells. It is unknown how outer hair cells normally respond while constrained by the organ of Corti, the physiologically appropriate condition. The proposed work first provides a preparation of the organ of Corti that allows study of hair cells in their physiologically correct configuration. Then, the study addresses two topics. (1) We will measure the mechanical response of outer hair cells embedded in the organ of Corti while accurately controlling their membrane potential. (2) Variable loading of a hair bundle will demarcate different mechanical behaviour. These experiments will provide an innovative approach to the cellular basis of cochlear processing.