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PhD student - Cancer Immunotherapies

Applications Close : 04 June 2021

Job Description

PROJECT TITLE

Immune regulation through bi-directional interactions between subsets of Natural Killer cells and Dendritic cells.

ABOUT THE PROJECT

This project will investigate interactions between two immune cell types: natural killer (NK) cells and dendritic cells (DCs). NK cells play an essential role in the early detection of infections or malignant transformation while DCs initiate and direct immune responses. Evidence for bi-directional interactions between NK cells and DCs has been provided in the early 2000s. Since then, our knowledge of NK cell and DC diversity has considerably increased. NK cells and DCs can no longer be considered as homogenous populations up to 30,000 phenotypic populations identified by mass cytometry in one individual [1] while four main human DC subsets have been described:  monocyte-derived DCs, plasmacytoid DCs and type 1 and 2 conventional DCs [2]. Currently, we don’t know which NK subset(s) interact with which DC subset(s).

This project aims to provide a better understanding of the crosstalk between distinct NK cell and DC subsets. Specific interactions between human cell subsets in response to different stimuli will be investigated in vitro and in vivo. The candidate will have access to state-of-the-art technology including high-parameter flow cytometry (BD Fortessa and BD FACSymphony analysers) as well as cutting-edge humanised mouse models [3, 4]. By addressing an important knowledge gap in the field, this project will lay the foundation for preclinical research in a wide range of pathologies including cancer, infectious diseases and autoimmune disorders.

SCHOLARSHIP

The candidate will be enrolled in the PhD program at the University of Queensland and will receive a UQ PhD Scholarship. Stipend is valued at $28k per annum for 3 years.

https://future-students.uq.edu.au/study/programs/doctor-philosophy-7501

THE TEAM

The project will be performed in the Cancer Immunotherapies laboratory at Mater Research, located at the Translational Research Institute in Brisbane. https://www.materresearch.org.au/Our-research/Research-programs/Research-Group?group=117

Our laboratory is composed of 3 postdoctoral fellows, 1 research assistant and 1 PhD student. You will be directly supervised by Dr Camille Guillerey. https://www.tri.edu.au/staff/camille-guillerey

We have extensive expertise in dendritic cell research [3-6] and NK cell research [7-10]. In addition, we have developed a unique preclinical model called humanised mice which allow the study of human immune cell interactions in vivo [3, 4]. Our group has an interest in cancer immunotherapies, and more particularly childhood leukaemia. We aim to provide a better understanding of immune responses to cancer and to translate it into new therapies for cancer patients.

REFERENCES

1. Horowitz, A., et al., Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci Transl Med, 2013. 5(208): p. 208ra145.

2. O'Keeffe, M., W.H. Mok, and K.J. Radford, Human dendritic cell subsets and function in health and disease. Cell Mol Life Sci, 2015. 72(22): p. 4309-25.

3. Pearson, F.E., et al., Activation of human CD141(+) and CD1c(+) dendritic cells in vivo with combined TLR3 and TLR7/8 ligation. Immunol Cell Biol, 2018. 96(4): p. 390-400.

4. Ding, Y., et al., FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo. J Immunol, 2014. 192(4): p. 1982-9.

5. Chiang, M.C., et al., Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets. Eur J Immunol, 2016. 46(2): p. 329-39.

6. Tullett, K.M., et al., Targeting CLEC9A delivers antigen to human CD141(+) DC for CD4(+) and CD8(+)T cell recognition. JCI Insight, 2016. 1(7): p. e87102.

7. Guillerey, C., N.D. Huntington, and M.J. Smyth, Targeting natural killer cells in cancer immunotherapy. Nat Immunol, 2016. 17(9): p. 1025-36.

8. Guillerey, C., et al., Pivotal role of plasmacytoid dendritic cells in inflammation and NK-cell responses after TLR9 triggering in mice. Blood, 2012. 120(1): p. 90-9.

9. Stannard, K.A., et al., Human peripheral blood DNAM-1(neg) NK cells are a terminally differentiated subset with limited effector functions. Blood Adv, 2019. 3(11): p. 1681-1694.

10. Guillerey, C., et al., Toll-like receptor 3 regulates NK cell responses to cytokines and controls experimental metastasis. Oncoimmunology, 2015. 4(9): p. e1027468.

Required Skills

Please note that due to current travel restrictions, we will only accept candidates (Australian and international) who are currently in Australia.

Applicants must hold a Bachelor’s or equivalent science or medicine degree with first-class Honours, and/or a distinction in a research Masters degree in a relevant discipline (e.g. Immunology, cell biology).

The candidate should have:

  • Excellent written and verbal English;
  • The proven ability to work both independently and as part of a team;
  • Honours I (or equivalent) and/or Masters with outstanding thesis grade or Coursework Masters with outstanding performance, particularly in research related courses.
  • Demonstrated outstanding academic achievement as evidenced by high CGPA, rank within class, academic prizes and awards
  • Strong wet lab skills (e.g. cell cultures, assays such as ELISA, ELISPOT). Experience in flow cytometry and/or with mouse handling would be advantageous
  • A candidate will perform animal work, prior experience advantageous but not essential.

For further details contact

Camille Guillerey

Email: [email protected]

Phone: 07 344 37519


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