Call for applications
for 2 scholarships for 2 doctoral projects
in Parasitology / Immunology / Veterinary Medicine in Berlin!
Please read carefully the requirements, see below!!! We cannot consider incomplete applications!
The Research Training Group 2046 is a Berlin-based doctoral program for research in parasitology, veterinary medicine, and immunology. We offer 2 scholarships for 2 PhD students, each funded by the Einsteinstiftung for 3 years. The projects are located at the Freie Universität Berlin, Dept. of Veterinary Medicine in Düppel. Preferred project start will be January 1, 2021.
Project description: PhD student 1
The intestine is a key organ for many chronic inflammatory diseases. Here, numerous functions of digestion, the regulation of the immune system and the microbiome are interconnected. The ubiquitous intestinal roundworm Ascaris spp. infects humans and livestock alike and belongs to the intestinal microbiome. While the immune system usually tolerates irrelevant stimuli ("immune tolerance"), in chronic inflammatory diseases such triggers lead to inflammation. In industrial and developing countries inflammatory bowel diseases (IBD: Crohn's disease, ulcerative colitis) are significantly on the rise. The incidence of these diseases is particularly high among young individuals (15 to 35 years). In parallel, Ascaris infections in humans and pigs are common in young individuals/pigs and childhood exposure to Ascaris may foster immune education and the appropriate instruction of immune tolerance.
Aim of the project is to understand how Ascaris and gut microbes synergize in promoting gut health, this project aims to characterize the adaptive T cell responses to Ascaris and gut microbes in Ascaris-infected humans as well as pigs.
The work program comprises:
- Human and gut porcine microbial signatures during Ascaris infection
- Number, phenotype and function of circulating blood CD4+ T cells reactive against Ascaris antigen (excretory/secretory products of larval and adult stages), prominent commensals / pathogens (e.g. E. coli, Lactobacillus, Bifidobacteria, Bacteroides, Salmonella typhimurium, Clostridium difficile)
- in Ascaris-infected individuals versus endemic normal (peripheral blood)
- in Ascaris-infected / naive pigs with and without induction of TNBS-induced colitis (peripheral blood and intestine)
- IgA / IgE response against Ascaris and gut microbes
- Effect of microbial metabolites and Ascaris ES products on immune cells (regulatory dendritic cells and monocytes / macrophages) in humans and pigs
- Intestinal barrier integrity and defense program of intestinal epithelial and immune cells in healthy versus Ascaris-infected pigs: metabolic activity, mucus viscosity and NAD(P)H fluorescence lifetime imaging (FLIM) (cooperation with Raluca Niesner, Berlin)
Midha A et al. 2020.Trilateral relationship: Ascaris, Microbiota and host cells. Trends Parasitol, doi: 10.1016/j.pt.2020.09.002.
Midha A et al 2018. The intestinal roundworm Ascaris suum releases antimicrobial factors which interfere with bacterial growth and biofilm formation. Front Cell Infect Microbiol, doi: 10.3389/fcimb.2018.00271.
Hegazy AN et al. 2017. Circulating and tissue-resident CD4 + T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology, 153:1320-37.
Project description: PhD student 2
Currently, the possible interactions between helminth infection and the outcome of viral pneumonia are intensively discussed. On the one hand, systemic immunomodulatory effects of helminths (e.g. IL-10 and Treg induction, alternatively activated macrophages (AAMs)) and the type 2 (Th2) skewed host immune response capable to suppress type 1 immunity might moderate pulmonary inflammation. On the other hand, pulmonary pathology is associated with eosinophil infiltration and lung fibrosis mediated by perivascular infiltrating AAMs, both being hallmarks of the helminth-induced immune response.
For Ascaris, being one of the most common human intestinal parasites, this topic can be studied experimentally in pigs - the natural hosts for zoonotic Ascaris suum. Upon infection, Ascaris larvae start tissue migration through liver and lungs and induce acute lung pathology before establishing chronic infection in the gut. Hence this project will exploit the dual roles of Ascaris infection - acute larval lung injury and chronic, immunomodulatory intestinal infection - on the outcome of pneumonia.
Perspective for human medicine: Experimental pig infections allow us to study the tissue-specific but also systemic pathogen-specific T helper cell responses that orchestrate pathogen control and possibly indicate disease severity and parasite burden. This knowledge on blood-derived, pathogen-specific Th cell phenotyping can be applied and transferred to helminth-endemic regions.
Bradbury RS et al. 2020. Will helminth co-infection modulate COVID-19 severity in endemic regions? Nat Rev Immunol, 20:342.
Hays R et al. 2020. Helminth coinfection and COVID-19: An alternate hypothesis. PLoS Negl Trop Dis, 14:e0008628.
Schmidt S et al. 2020. The domestic pig as human-relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus. Eur J Immunol, 10.1002/eji.201948524.
Braun J et al. 2020. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature, 587:270-4, doi: 10.1038/s41586-020-2598-9.
Le Bert N et al. 2020. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature, 584:457–62.
We are looking for highly motivated PhD candidates who are strongly committed to research. Candidates must
hold a Master’s or similar degree (e.g. Staatsexamen Tierarzt, DVM) in a relevant subject, must have significant
laboratory experience in Parasitology and / or Veterinary Medicine, and speak English on B1 level. Candidates
should be interested in fieldwork in Africa, because parts of the projects will be done in Kenya in cooperation with
the KEMRI Wellcome Research Programme.
We expect at minimum a complete Curriculum Vitae including all relevant certificates, two reference letters by two different referees and a letter of motivation (including why you want to work in Parasitology, why you want to work in these projects; future career plans). Send your application as one PDF e-mail attachment via E-mail only to email@example.com, subject: Application Einstein PhD student scholarships. Please note: incomplete applications cannot be considered
This call will close on 10.12.2020. Interviews will take place likely ONLINE before Christmas.UPDATE:
Process of evaluation: Complete applications will be evaluated and principal investigators will choose the candidates for the interviews. Interviewes will be likely on December 21, 2020, but the date is not yet confirmed. During the interview sessions, selected candidates need to give a 7 min. talk introducing their most recent research. Candidates will have discussions with a panel of PIs and individual interviews with the potential supervisors.
For any questions, please refer to firstname.lastname@example.org.