This is a full-time, fixed term (4 years with the possibility to extend to 5 years) role for 3x positions on Crick terms and conditions of employment.
3 Wellcome Trust funded postdoctoral research posts (in one of immunology, cell biology, and computational biology) in the laboratory of Moritz Treeck (www.treecklab.org) are available. We are looking for highly motivated researchers to investigate the complex interaction of effector proteins that one of the most successful parasite, Toxoplasma gondii, injects into its host cells. Toxoplasma is remarkable for a pathogen, as it is a true generalist that infects any nucleated cell of any warm-blooded animal, including ~30% of the human population. To do that, the parasite secretes effector proteins into the host cells to rewire their normal behaviour in the parasites’ favour, ranging from the cell autonomous immune response within the infected cell to altered cytokine secretion, thus creating a favourable infection environment.
Only a few of the ~220 predicted effector proteins and their effects on the host have been characterized, often leading to important and novel insights into host-pathogen interaction. However, the majority of the effectors are of unknown function and hold great promise to uncover novel mechanisms as to how the parasite subverts the host immune response. The aim of this project is to identify novel effectors that act on the host cell transcriptional response in various cell types and species in a high-throughput fashion. Novel methods have been developed in the lab to address this question, such as the PerturbSEQ technology that combines parasite CRISPR screens (Young J, et al., 2019, PMID: 31481656) and single-cell RNAseq experiments of the infected host cell. The mechanism by which the novel effector proteins function will be studied using both cell culture and murine in vivo systems, with a major focus on those that affect the overall immune response of the host in a paracrine manner. Ultimately, we aim to identify and characterise all effector proteins that Toxoplasma exports into various host cells of assorted species which alter the host transcriptional response.
To perform this work, we are looking for 3 motivated postdocs with a strong interest in infection biology and host-pathogen interaction. We are particularly interested in hearing from candidates with a background in either of the following:
- Cell biology of the immune cell/host cell. A good mechanistic understanding of transcriptional regulation of (immune) cells is essential. Experience using reporter assays of cellular responses to infection or stimulation (cytokine secretion, changes in transcriptional activity) and host cell genetic modifications (RNAi, conditional gene deletion or knock-down) is desirable. Experience working with several cell types from various species is also desirable.
- Cellular immunology of the innate immune system. A very good understanding of the murine innate immune system and how its components function together is essential (cell types, cytokine and chemokine biology). Experience in working with mice is essential. Very good knowledge of infection biology in the context of the murine host is a plus.
- Computational biology. A solid background in bioinformatics/statistics and enthusiasm to tackle highly complex biological problems is essential. Experience in analysis of single-cell sequencing data would be a plus, as would experience in cluster-based computing. The primary role will be to develop analysis methods for multi-model single-cell sequencing in a novel host-pathogen interaction context, but there may also be opportunities to be involved in wet-lab data generation. This position will be co-supervised by Prof. Manfred Claassen, a specialist in advanced single cell analysis methods (https://www.medizin.uni-tuebingen.de/de/das-klinikum/mitarbeiter/profil/2147).
The project complements ongoing research in the lab to identify effector proteins of the parasite which are essential for survival within an infected cell. Within the lab, we foster a diverse group of scientists coming from various scientific backgrounds and employ a range of techniques to answer our questions including quantitative proteomics, CRISPR screens, single-cell RNA seq, immunology, cell biology and biochemical methods. See www.treecklab.org for an overview of the lab and projects. For the computational part of this work, we closely collaborate with the laboratory of Prof Manfred Claassen at the University of Tuebingen, who applies machine learning methods to complex single cell analysis. As such, we have a diverse team of like-minded scientists that can learn from each other and tackle questions in a collaborative and fun way, while providing substantial room to build an independent niche within the team.
The Crick has a wide research portfolio. Since there are no divisions or departments, our research groups have the freedom to establish research programmes within broad areas. We are collaborative and outward-looking, reflecting our status as a partnership of six organisations aiming to pool knowledge, ideas and resources.
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- If you are interested in applying for this role, please apply via our website.
- A cover letter detailing for which of the 3 positions you are applying for and how your research skills and interests align with the aims of this project is absolutely essential.
- There is no closing date: positions will be filled when a suitable candidate has been identified. The anticipated start is from February 2022. Later, or earlier start dates are possible.
Interested candidates are encouraged to enquire whether the position of interest is still available.
- All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.
- Informal requests can be made to firstname.lastname@example.org
Essential Qualifications, experience and competencies
- PhD in a field related to the above, or in the final stages of PhD submission
- Good knowledge and experience in a field as described above
- Technical expertise in a field as described above
- Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals.
- Evidence of data presentation at scientific meetings
- Experience of experimental design
- Ability to work independently and also capable of interacting within a group