Objectives:

• Profile epigenomes of intestinal tissue-resident memory T cell subsets
• Unravel which genes are epigenetically imprinted in a microbiota-dependent way and identify microbiota-derived signals involved using murine models
• Analyse role of stromal cells for the induction of intestinal tissue-resident memory T cells

Results:

• Generate and bioinformatically analyse whole-genome DNA methylation, ATACseq and RNAseq data from intestinal tissue-resident memory T cell subsets
• Define microbiota-dependent and disease-associated epigenetic signatures as biomarkers
• Dissect role of stromal cells for intestinal T cell priming

Secondments:

• Erasmus University Medical Center (Rotterdam, Netherlands): isolation of human intestinal T cells from IBD patients
• QIAGEN (Aarhus, Denmark): analysis of NGS data
• Radboud University Medical Center (Nijmegen, Netherlands): integration of multi-omics data

Requirements:

• Solid background/expertise in cellular & molecular immunology
• Interest in computational biology and ‘big data’ analysis
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be, in line with the HZI regulations for the duration of a PhD study, extended up to one year according to the employment rules of the HZI. The PhD student will become member of the HZI Graduate School, will be expected to present her/his work annually at its conferences and to follow its training program.

Objectives:

• Determine CD4 lineage-dependent epigenetic and transcriptional signatures in naïve and memory CD8⁺ T cells under homeostatic and (auto)inflammatory conditions
• Characterization of mouse and human innate-like CD8⁺ T cells and their shaping by NKT2 cells

Results:

• scRNAseq and ATACseq data from naïve and memory CD8⁺ T cells (in absence/presence of CD4 lineage T cells)
• Transcriptional signatures of human innate-like CD8⁺ T cells

Secondments:

• University of Tartu (Estonia): Isolation of human innate-like memory CD8⁺ T cells
• QIAGEN (Aarhus, Denmark): analysis of NGS data and integration of mouse and human NGS data

Requirements:

• Solid background/expertise in cellular & molecular immunology and/or molecular biology
• Interest in computational biology and ‘big data’ analysis
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years. The PhD student will become a member of the MUW PhD program Immunology and will be expected to follow its training program.

Objectives:

• Dissect the impact of specialized antigen presenting cells in distinct anatomical niches on T cell fate decisions in tolerance and autoimmunity

Results:

• Generate and bioinformatically compare T cell repertoires in mouse models harboring genetically manipulated antigen presenting cell (APC) subsets
• Identify T cell specificities that selectively disappear or undergo distinct cell fates depending on the manipulation of a given APC subset
• Physically follow the fate and pathogenic potential of distinct T cell specificities though re-expression of candidate T cell receptors in retrogenic- or transgenic mice

Secondments:

• QIAGEN (Aarhus, Denmark): analysis of T cell repertoires

Requirements:

• Background in cellular & molecular immunology
• Interest in computational biology
• Motivation to work in an international team

Appointment:

The duration of the appointment as a Marie Curie ITN fellow will initially be for a period of 3 years and can, in line with the Graduate Center^LMU regulations for PhD studies, be extended for up to one year. The PhD student will become an associated member of the Integrated Research Training Group (IRTG) of the CRC 1054, which offers training in general immunology, cutting-edge technologies, statistical analyses and soft-skills. The PhD student is expected to present her/his work on a regular basis and to follow the IRTG training program.

Objectives:

• Identify key transitions and intermediate differentiation steps in development of T_RM and T_FR cells
• Assess the impact of metabolic changes on cell specialisation and activity

Results:

• scRNAseq data describing the transition of T_FH to T_FR cells in GCs, and effector CD8⁺ T cells to intestinal T_RM cells along a pseudo time;
• Refinement of analysis with super-imposition of ATACseq and mitochondrial proteomics datasets from key differentiation stages
• Combining gene expression data and metabolic pathways

Secondments:

• SANGER (Cambridge, UK): Analysis of NGS and proteomic data, data integration and construction of scRNAseq pseudo timelines
• BAYER (Wuppertal, Germany) Study human T cells to validate our data sets in humans

Requirements:

• Solid background/expertise in in computational biology and ‘big data’ analysis
• Strong interest in cellular & molecular immunology
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be extended up to one year. The PhD student will enroll at iMM and in the Lisbon Academic Medical Centre (CAML) PhD programme that runs since 2010. The CAML, composed by the Lisbon School of Medicine, the iMM and Santa Maria University Hospital, encourages new collaborative approaches and more effective communication between basic and clinical researchers. The PhD programme focuses on research projects of excellence and has a flexible and modular advanced training component:
PhD fellows are followed up by a Thesis Committee, responsible for monitoring and analysing the progress made by the students, and includes the supervisor, another expert in the research area, and the Tutor, chosen by the student among the senior researchers. The Tutor has the role of accompanying the institutional integration and the development of the student's scientific culture. PhD students at iMM are strongly encouraged to participate and to organize activities that contribute to the lively iMM scientific environment. With the support of the iMM Training Hub, PhD students organize the Annual Scientific Meeting, the Annual Retreat, Workshops, Pizza seminars and other community building activities. Once enrolled at iMM, students also attend mandatory induction sessions that include organisational aspects of iMM; quality management requirements and safety regulations.

Objectives:

• Determine the role of cellular metabolism in early colonization of tissue-resident Tregs using genetically modified mice.
• Analyze the role of cellular metabolism in adaptation of tissue-resident Tregs in health, cancer and autoimmunity using genetically modified mice.
• Analyze ontogeny, migration, retention and stability of tissue-resident Tregs

Results:

• Identification of molecular mechanisms involved in early colonization of tissue-resident Tregs by performing multiparametric flow cytometry, RNAseq and ATACseq.
• Identification of molecular mechanisms involved in adaptation of tissue-resident Tregs during inflammation by generating multiparametric flow cytometry, RNAseq and ATACseq.

Secondments:

• Medical University of Vienna (MUW, Vienna, Austria): Generation of epigenetic data
• Institute of Molecular Medicine (IMM, Lisbon, Portugal): Defining transcriptomic and epigenetic signatures of tissue-resident Tregs.
• QIAGEN (Aarhus, Denmark): Analysis of NGS data

Requirements:

• Solid background/expertise in cellular & molecular immunology
• Interest in computational biology and ‘big data’ analysis
• Skills to interact easily in a group and to communicate

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be extended to one more year according to the employment rules. The PhD student will become a member of the Sorbonne University Graduate School, and thus will present her/his work annually at its conferences and follow its training program.

Objectives:

• Investigate whether autoimmune signatures can predict clinical outcome in cancer patients receiving PD1/CTLA-4 immunotherapy
• Test if changes in CD38⁺ mucosal T cells predict subsequent gastrointestinal adverse events
• Investigate link between the CD28 pathway and checkpoint blockade-induced autoimmunity

Results:

• High-dimensional cytometry data encompassing multiple immune cell populations
• Analysis of liver/gut samples from individuals developing autoimmune hepatitis/colitis following checkpoint immunotherapy
• RNAseq of T cell subsets from individuals showing good or poor clinical responses

Secondments:

• Erasmus University Medical Center (Rotterdam, Netherlands): specialist training in flow cytometric detection of mucosally-imprinted T cells
• IBM (Ruschlikon, Switzerland): mathematical models and deep-learning approaches to integrate experimental and clinical data

Requirements:

• Strong background/expertise in cellular & molecular immunology
• Interest in computational biology and ‘big data’ analysis
• Open to multi-disciplinary training

Appointment:

The successful applicant will be offered a 3 year appointment at UCL with potential for extension. They will become a member of the UCL Doctoral School, and have access to a wide range of training opportunities through the Doctoral Skills Development programme. Regular presentation and networking opportunities will be provided via Institute-wide meetings and the annual PhD colloquium.

Objectives:

• Develop high-dimensional flow cytometric panels for routine assessment of modulated T cell and lymphoid progenitor cells in several species and organs of preclinical toxicological relevance
• Generate tool to predict safety in preclinical species before clinical applications (‘First in Human’)

Results:

• Define tools for a better prediction of immunotoxicological risks in ‘First in Human’ studies based on correlations of immune cell population frequencies, phenotypes, and functions in several organs of different species (rat, cynomolgus monkey, human)

Secondments:

• Miltenyi Biotec (Bergisch-Gladbach, Germany): optimisation of marker panels for several species and tissues based on Miltenyi’s expertise in antibody development
• University College London (UK): multi-parametric flow cytometry analysis of healthy donors and patients receiving checkpoint immunotherapy; patient cohorts
• University of Turku (Finland): bioinformatic analysis of multiplex data and machine-learning approaches for correlation of species-specific patterns

Requirements:

• Solid background/expertise in cell biological techniques, flow cytometry and immunology
• Interest in ‘big data’ analysis

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years.

Objectives:

• Study the epigenetic control of co- inhibitory receptor TIGIT expression, a potential therapeutic target, in CD4⁺ effector/memory T cell subsets
• Define how TCR-dependent and co-stimulatory signals modulate TIGIT expression and subsequent function of CD4⁺ effector/memory T cell subsets in intestinal (auto) immune diseases
• Assess role of microenvironmental cues (e.g. nutrition, vitamins, microbiota) and immunosuppressive medication in modulation of TIGIT expression
• Modulate TIGIT expression to inhibit intestinal inflammation and (auto) immunity

Results:

• DNA methylation status of TIGIT in human T cell subsets
• Impact of DNA methylation on TIGIT expression; identification of TCR-dependent and environmental-derived signals that induce and maintain TIGIT expression
• Definition of microenvironmental conditions to fine-tune TIGIT expression during inflammatory and (auto)immune responses in the intestine

Secondments:

• Helmholtz Centre for Infection Research (Braunschweig, Germany): DNA methylation analyses to get insights into the epigenetic mechanisms controlling TIGIT expression
• University College London (UK): analysis of TIGIT+ cells in patients during checkpoint inhibitor treatment to broaden the conditions tested as tumor microenvironmental cues are the exact opposite from chronic inflammatory cues
• Hycult Biotech (Uden, The Netherlands): development of an antibody-based assay for the detection of TIGIT

Requirements:

• Solid background/expertise in cellular & molecular immunology
• Interest in computational biology and ‘big data’ analysis
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be, in line with the ERASM regulations for the duration of a PhD study, extended up to one year according to the employment rules of the ERASM. The PhD student will become member of the ErasmusMC Graduate School for Molecular Medicine and will be expected to present her/his work annually at its conferences and to follow its training program.

Objectives:

• Identify age-related epigenomic and transcriptomic signatures of T cell subsets in mouse and human blood and tissues
• Analyze T cell changes in chronic inflammatory and autoimmune diseases as well as in cancer patients treated with checkpoint inhibitors
• Analyze the mechanistic role of epigenomic and transcriptomic changes in T cells

Results:

• Transcriptomic and epigenetic profiles of selected T cell subsets (scRNAseq, ATACseq, bisulfite amplicon sequencing, TCR repertoire analysis) in aging and diseases associated with chronic inflammation.
• Epigenetic biomarkers to count inflammation–associated T cell numbers in chronic inflammatory and autoimmune diseases, and as treatment outcomes (cancer)

Secondments:

• Babraham Institute (Cambridge, UK): analysis of patient cohort samples
• InSCREENeX (Braunschweig, Germany): studies on tissue-related factors

Requirements:

• Solid background in molecular biology and immunology
• Experience or interest in R-language and data analysis
• Ability to work with several projects in parallel

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and the duration of a PhD study can be extended up to one year in line with the UTARTU regulations. The PhD student will become member of the UTARTU Medical Faculty Graduate School. The student will be expected to follow graduate school’s training program, to publish 3 research papers, and to present her/his work at annual attestations and graduate school conferences.

Objectives:

• Profile antigen-specific lung and lymph node CD4 ^{T cell subsets to determine how location alters the properties of helper T cells}
• In vivo CRISPR screen of lung homing molecules
• Develop mathematical model of selection in lung GCs
• Analyse human lung transcriptomic data sets from inflammatory and autoimmune conditions to identify specific signatures of ectopic lymphoid structures

Results:

• scRNAseq data of helper T cells in lymph nodes and lung
• Dissect differences of T cell help in lung and secondary lymphoid tissues
• Identify adhesion and chemokine receptors responsible for ectopic GC formation and maintenance

Secondments:

• IBM Research (Rüschlikon, Switzerland): analysis of scRNAseq data
• Helmholtz Centre for Infection Research (Braunschweig, Germany): in silico modelling of ectopic GCs

Requirements:

• Solid background/expertise in cellular & molecular immunology
• Interest in computational biology and ‘big data’ analysis
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years. The PhD student will become member of the University of Cambridge PhD programme, will be expected to present her/his work annually at its conferences and to follow its training program.

Objectives:

• Develop optimised algorithms for molecular signature identification, with focus on single-cell transcriptomics, epigenomics and proteomics data
• Utilise machine learning and predictive modelling of disease and treatment risks, with a focus on autoimmune side-effects of checkpoint immunotherapy
• Make new computational tools available as easy-to-use software packages

Results:

• New computational tools for analysing high-dimensional molecular data
• Experimentally testable computational predictions and hypotheses about disease outcome and treatment risks of checkpoint immunotherapy

Secondments:

• University College London (London, UK): autoimmune side-effects of checkpoint immunotherapy
• IBM (Zurich, Switzerland): machine learning

Requirements:

• Solid background/expertise in bioinformatics, biostatistics or machine learning
• Good programming skills (e.g. Python, R)
• Abilities to work in a multidisciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be, in line with UTU regulations for the duration of a PhD study, extended up to one year according to the employment rules of UTU. The PhD student will become member of the UTU Graduate School, will be expected to present her/his work annually at its conferences and to follow its training program.

Objectives:

• Develop multi-scale models of T cell-mediated immunity that combines intracellular factors, microenvironmental cues and important cytokines through ordinary differential equations and/or stochastic models.
• Couple T cell models with existing models of B cell dynamics.
• Develop hybrid AI models to predict the T cell receptor affinity to epitopes.
• Characterise the role of autoreactive T cells in autoimmune diseases.

Results:

• Multi-scale model of T cell maturation and differentiation into different effector cell types.
• Multi-dimensional clustering techniques to identify cellular populations in single-cell T cell data.
• Hybrid models to jointly describe B and T cell dynamics.

Secondments:

• SANGER (Teichmann: analysis of single-cell genome, epigenome and transcriptome data;
• BI (Linterman), characterisation of scRNAseq from GCs;
• HZI (Meyer-Hermann) M30-31, multi-scale modelling of T cell responses using HZI’s expertise on GC modelling

Requirements:

• Solid background/expertise in cellular & molecular immunology
• Interest in computational biology and ‘big data’ analysis
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be, in line with the IBM regulations for the duration of a PhD study, extended up to one year. The PhD student will become a member of the Zurich Graduate School (either at ETH or University of Zurich), will be expected to present her/his work annually at its conferences and to follow its training program.

Objectives:

• Study CD4⁺ T cell states across human tissues by data mining the Human Cell Atlas data, both from within SANGER and from international Human Cell Atlas consortium (www.humancellatlas.org)
• Compare CD4⁺ T cell data across human tissues in both adult and fetal development
• Relate T cell states to tissue microenvironment (scRNAseq data for around 20 tissues should be available by 2020)
• Compare human data to mouse resources such as the Tabula Muris and Mouse Cell Atlas

Results:

• Comprehensive molecular understanding of CD4⁺ T cell states at single-cell resolution, during development and adult homeostasis
• Lymphoid and non-lymphoid tissue-specific cell states versus circulating blood cell states, with implications for cell-based therapies
• Similarity between data from mouse and human T cells, and with value for understanding the accuracy of mouse models for immunemediated diseases

Secondments:

• University College London (UK): generate single-cell genome and transcriptome data from human T cell subsets for cross species comparison
• IBM Zurich Laboratory (Switzerland): analysis of single-cell data using IBM’s expertise in AI and machine learning

Requirements:

• N/A

Appointment:

A Marie Curie ITN fellow for a maximum period of 3 years, which can be extended by a further year in line with Sanger and UoC regulations of PhD study. The Sanger student will be asked to present their work regularly and follow the Sanger training program, as well as attend further training at UoC.

Objectives:

• Develop solutions for identification of epigenetic signatures in T_RM cell subsets, with focus on ATACseq protocols and data analysis pipeline; extend current solutions for Biseq, RNAseq and TCRseq to single-cell analysis; develop solutions for Hi-C analyses

Results:

• Generation of Bi-seq and RNA-seq data from ex vivo isolated helper T cell subsets
• Full ATACseq analysis pipeline
• Full single-cell analysis solution
• Hi-C 3-dimensional visualisation tool
• Tools for bridging epigenetic and transcriptional datasets

Secondments:

• Instituto de Medicina Molecular (Lisbon, Portugal): generation of RNAseq and ATACseq data from various T_RM cell subsets for pipeline development
• Ludwig-Maximilians-University (Munich, Germany): generation of TCRseq data from thymic T cell subsets for validation of newly developed pipelines

Requirements:

• Solid background/expertise in Bioinformatics, Artificial Intelligence or Machine Learning
• Abilities to work in a multi-disciplinary environment

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be, in line with the UTARU regulations for the duration of a PhD study, extended up to one year according to the employment rules of the UTARU. The PhD student will become member of the UTARU Graduate School, will be expected to present her/his work annually at its conferences and to follow its training program. The ITN fellow will be based at QIAGEN Aarhus and participate in the single cell software development efforts here.

Objectives:

• Identify transcriptome dynamics in human T cells in response to pathogens; define response-eQTLs and reconstruct causal networks; assess the impact of host non-genetic factors (e.g. gender, age and microbiome) on genetic regulation of gene expression; build prediction models for immune response to stimulations; validate identified driver gene(s) in independent stimulation cohort and experimentally

Results:

• scRNAseq data from stimulated samples; genetic regulatory network in response to stimulation and causal candidate genes; marker genes of T cells for immune response to stimulations; computational models for prediction of immune responses

Secondments:

• HZI (Huehn) experimental validation of causal candidate genes for regulating immune responses using HZI’s expertise to manipulate primary T cells with CRISPR-Cas9;
• INSERM (Salomon) experimental validation of identified driver gene(s);
• IBM (Martinez): improvement of predictive models

Requirements:

• Excellent skills in computer programming (e.g. R, JAVA, Python), experience with different operating systems (Linux, Windows)
• Excellent English communication skills (written and spoken)
• Ability to work independently and as part of an international team

Appointment:

Based on a full-time appointment, the duration of the appointment as a Marie Curie ITN fellow will be for a maximum period of 3 years and can be, in line with the Radboud UMC regulations for the duration of a PhD study, extended up to one year according to the employment rules of the Radboud UMC.