Job Description

The Francis Crick Institute PhD programme recruitment is now live and this year our lab is recruiting! If you are interested in studying immune responses to tuberculosis in the human alveoli please apply- info in the link below. The Crick is a very inspiring place to do a PhD with an outstanding academic programme.

Project background and description

Tuberculosis (TB) remains an important global challenge in human health. The obstacles that make TB hard to eradicate are intrinsically linked to the intracellular lifestyle of Mycobacterium tuberculosis (Mtb). To cause disease and disseminate to other hosts, Mtb needs to replicate within human cells [1]. Our ultimate goal is to understand TB pathogenesis at the cellular level, which we believe is critical to design rational interventions.

Our group have established the use of human induced pluripotential stem cells (iPSC)-based models to study innate immune mechanisms in human macrophages at the molecular and cellular level [2, 3]. We combined these technologies with lung-on-chip approaches to mimic human alveolar environments and study early stages of TB [4]. Immunocompetent and experimentally accessible alveolar systems to study human respiratory diseases such as TB are lacking. We developed a unique single donor human induced pluripotent stem cell (iPSC)-derived Lung-on-Chip (iLoC) containing Type II and I alveolar epithelial cells, vascular endothelial cells, and macrophages in a microfluidic device that mimic the lung 3D mechanical stretching and air-liquid interface [4]. 

The potential PhD project will use genetic and imaging tools combined with organ on chip technologies to investigate the pathogen (Mtb) and the host cell factors that contribute to membrane damage and repair during infection. This project will capitalise on the iLoC to study early events of Mtb infection in the human alveolus. We have identified key pathways triggered in lung cells by the infection. This project will test how these pathways operate in multicellular environments in response to the infection. Our iLoC allows for experimental approaches to study cell type specific responses (e.g. by only incorporating one cell type genetically modified- knockout or knock in). We will combine the iLoC with genome edited iPSC to investigate innate immune pathways relevant in epithelial cells, endothelial cells and macrophages [5]. The choice of the specific project (pathways) will be decided in consultation with the candidate considering interests and background. We expect the student to capitalise on our unique settings to perform high resolution imaging of live Mtb in Biosafety level 3 (BSL3).