Project 2

Is targeting WT-histone H2A, H3 and H4 sufficient to neutralize NETs and tackle sepsis?

Host institute: Universität Münster, Germany (WWU)
Supervisor: Prof. Oliver Soehlein (WWU)
Co-supervisor: Dr Gerry Nicolaes (UMA)

Objectives
1. To systematically investigate the cytotoxicity of histone H1, H2A, H2B, H3 and H4 including WT- and cit-Histone. 
2. To examine the requirements (key residues/domain) of the identified histones for expression of toxicity. The derived results of objectives 1 & 2 will assist the Doctoral Candidate of project 6 (DC6) to focus on the specific histone isotypes. 
3. To apply to the imaging probes (developed by DC6) to investigate translocation of the released histones during NETosis and to use as diagnostic tools for sepsis.

Expected Results
1. Identification of histone isotypes (expanding to new histone isotypes or confirming WT histone H2A, H3 and H4 are the major mediator inducing cell death) as drug targets to neutralize NETs.
2. Identification of binding mechanism and key residues mediating cell death.
3. Decipher the translocation mechanism of histones during the NET formation.
4. Successfully use the novel probes as diagnostic tools to measure the level of released histones in blood of sepsis patients and indicate the condition of sepsis.

Secondments
- UMA (3 months)
- IIBB (3 months)
- PharmaTarget (1 month)

Requirements
Qualifications: Master in Science (MSc) or Medical Doctor degree (MD) equivalent to 240 credits, Felasa certificate (or equivalent) preferred, English B2 or above. The chosen applicant will be processed through the university application system and require the institution board approval prior to acceptance for doctoral studies.
Experience: Minimum of four years undergrad studies within the field of biology, immunology, biomedicine, medicine, or similar. The applicant should have experience in different basic methodology within the research field.
Knowledge & skills: The applicant should have basic knowledge in how to conduct in vivo experiments on animal models and knowledge in basic statistics. Good knowledge in standard analytical methods (e.g. flow cytometry) and tissue processing (e.g. immunohistochemistry) is meritorious. Experience in animal experimentation is commendable. Willingnes to perform animal experiments is a must.
Abilities: In abundance to the aforementioned requirements, the applicant should possess the ability to successfully conduct literature studies i.e., retrieve, critically review, analyze, and summarize literature. The applicant should be fluent in English in both writing and speech and have good communication abilities. The ability to independently plan experimental studies is meritorious.
Attitude and disposition: The Praetorian MSCA doctoral network requires abundant traveling and social settings. The applicant should be willing to present research orally and in writing, socialize and network at meetings within the consortium but also at major international conferences and at the home institution. The applicant is expected to voluntary contribute to the science community including engaging in scientific communities and PhD-communities at Münster University.