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MACROPHAGES & INFECTION
Master / PhD student position: Investigating lung macrophage biology during infection; flexible start date Contact: Carolyn King, carolyn.king@unibas.ch Project background: A quarter of the world’s population is infected with Mycobacterium tuberculosis. Multidrug resistant bacterial strains are on the rise, and impoverished people with little access to long, expensive treatments continue to bear the brunt of TB disease. Renewed interest in the only known effective vaccine, Mycobacterium bovis bacillus Calmette–Guérin (BCG), stems not only from its apparent ability to induce innate immune cell training in monocytes and macrophages, but also from increased efficacy observed with mucosal over intradermal delivery. Our preliminary data reveal that mycobacterial infection induces significant alveolar macrophage (AM) depletion in humans, macaques and mice and that the level of depletion depends on the route of immunization and/or bacterial load. The goal of this project is to investigate the impact of mucosal vaccination on lung macrophage subtype remodeling and its relationship to BCG mediated protection in mice and humans. Short project description: The student will use high dimensional flow cytometry and R data analysis to understand how lung macrophages respond to mucosal versus subcutaneous BCG vaccination in mice. Macrophage localization will be investigated by combined fluorescence microscopy and in situ transcriptomics; distinct macrophage subsets will be isolated to assess their ability to phagocytose bacteria, control bacterial growth and produce cytokines. We offer: ● a highly collaborative, international and interactive environment ● opportunity to develop skills in flow cytometry, microscopy and many other immunology techniques ● a place to learn and advance as a scientist
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Doctoral and postdoctoral positions available starting in October 2022
T and B cell responses during pulmonary infection PhD project: Tissue resident memory (TRM) T cells play critical roles in tissue remodeling, repair and protection against subsequent infection. Poised to rapidly respond at the site of antigen exposure, TRM cells are an attractive therapeutic target for various immune interventions. We recently identified a population of lung resident T cells with high expression of HIF1α, a transcription factor that supports glycolysis and cell survival in oxygen/nutrient poor environments. This project focuses on understanding how HIF1α activity regulates the generation, localization and function of these tissue T cells, and further exploring a molecular link for T cell intrinsic iron metabolism in these processes. Postdoctoral project: Our recent work suggests that CD4 T cells that interact with B cells in the lung have a better chance of providing long-lasting protection against pulmonary infection compared to more inflammatory T helper cells. B cells act as integral hubs with wide-ranging effects in the immune network, but their impact in tuberculosis (TB) hasn’t been adequately assessed. The postdoctoral fellow will investigate the role of antibodies and tissue resident B cells during TB infection. Immunoproteomic approaches will be used to identify novel antibody targets and antibody glycosylation features during TB infection in mice. The function of TB-specific monoclonal antibodies isolated from both humans and mice will be further analyzed using in vitro and in vivo (adenoviral delivery in mice) approaches. These findings will be ultimately be integrated with extensive transcriptomic and spatial analysis of the pulmonary immune compartment during TB infection. The project was recently selected for ERC Consolidator funding (to be financed by Switzerland's State Secretariat for Education, Research, and Innovation). Required Qualifications for Doctoral Candidates:
Required Qualifications for Postdoctoral Candidates:
Important information:
To apply: Please send a cover letter describing research interests, career goals and a curriculum vitae to Carolyn King (email: carolyn.king@unibas.ch) A quick bit of good news - our grant, DEBATE (Deciphering the role of B cells and antibodies during tuberculosis) was positively reviewed by the ERC Council. This was a major team effort - thanks especially to David Schreiner, Clemens Hermann and Nivedya Swarnalekha - my dream team - for all their help with writing, thinking, experimenting and generally pulling it together in April 2021. It was worth it. Thanks also to the reviewers - for taking a chance on me/us. And now we move on - lots of exciting stuff coming up.
PS people interested in doctoral work or postdocs - we have open positions! I'd love to hear what you're interested in and how our lab might be a good fit for you! Welcome to two new graduate students: Wadschma Naderi and Nikos Pantouloufos. Wadschma will be studying B cell responses to mycobacteria infection while Nikos will expand on the macrophage work started by Mara and Maike. We are glad they could join us before Nivedya leaves in January to start a postdoctoral fellowsihp at Roche as part of immunology incubator with Nicolas Gagliani. This caps off an amazing year for Nivedya with a hard earned publication, successful PhD defense, postdoctoral fellowship award from the University and now a new job!!! Meanwhile, some other stuff is percolating; look forward to sharing our good news soon!
new lab members Amerbach prize Collaboration for TB vaccine discovery (CTVD), funded by the Bill & Melissa Gates foundation6/27/2021 We are slowly making "real" on our commitment to understanding the humoral response to TB infection, most recently by joining CTVD's B cells and antibody community (https://www.ctvd.co/Pages/default.aspx). And just in time - the annual meeting was held online on June 15/16. It's wonderful to be connected to so many outstanding scientists who are dedicated to promoting open and collaborative TB research.
Since March we have welcomed two new masters students - Mara Esposito and Namitha Putananickal. They are both studying MACROPHAGES!!!!!!! Mara is investigating pulmonary macrophage heterogeneity following mycobacteria infection and Namitha is studying how monoclonal antibodies to surface antigens on Mtb differential impact bacterial uptake and growth in alveolar versus bone marrow derived macrophages. Macrophages = new territory for the lab and we are learning a lot.
Clemens was awarded a competitive Marie Skłodowska-Curie award to study humoral immunity during BCG vaccination in humans and mice and is already well underway with the IMCB lab's team #tuberculosis.
Despite the craziness that continues in the US, 2021 is off to a pretty good start: we received some essential funding from the Helmut Horten foundation and our influenza/CD4 Trm story is officially published. Meanwhile, we are anticipating the arrival of Jean de Lima (Brazil) and Maike Erber (Germany) in the next few weeks, along with two new masters students who will work on macrophages and mycobacteria! I love how multinational academic labs are. With so much turnover, there will be a bit of 'down time' for the IMCB lab but we are revving up again!
Happy new year to anyone who reads this! Most importantly, we are all healthy and relatively happy (I think!). I'm super grateful to my team for making the IMCB lab the brilliant place it's meant to be - I couldn't have asked for a better group of people to 'science' with.
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CarolynMemory is the enemy of wonder Archives
November 2022
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