PhD fellowship in "Translational model of Vascular Occlusive Crisis in anaesthetised mice with Sickle Cell Disease" at the LIFEPHARM Centre

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen is offering a 3-year PhD fellowship commencing 1 March 2021 or soon thereafter.

The Faculty of Health and Medical Sciences and Novo Nordisk A/S established a research centre in 2010 - The LIFEPHARM Centre (www.lifepharm.dk) - with a total budget of DKK 78 million covering activities until the end of 2020.

The present position is part of the Centre´s activities. The purpose of the research centre is to strengthen the research in experimental pharmacology and toxicology and to increase the output of candidates and PhDs with a strong in vivo pharmacological profile.

It is expected that the future PhD fellow will be enrolled in the Graduate Programme for In Vivo Pharmacology and Experimental Animals (IVP) at SUND and participate actively in this network. The IVP Graduate Programme was established in 2006 as a collaboration between the Faculties of Life Sciences, Pharmaceutical Sciences and Health Sciences at the University of Copenhagen, University of Aarhus, and industrial partners; Novo Nordisk A/S, LEO Pharma and H. Lundbeck A/S. www.invivofarm.dk

For more information on LIFEPHARM or IVP please contact:
Professor Jens Lykkesfeldt
Director of LIFEPHARM
jopl@sund.ku.dk
Phone: (+45) 35 33 31 63

Project description

In this project, a murine model of Vaso-Occlusive Crisis (VOC) induction will be defined for study of VOC biology and identification of novel VOC biomarkers with potential human use. Painful VOCs are a hallmark clinical presentation in Sickle Cell Disease (SCD) patients. SCD (also known as Sickle Cell Anaemia) is a chronic recessive disease caused by mutations in the haemoglobin gene. Polymerisation of the mutated haemoglobin leads to deformation (i.e. sickling) of the red blood cells, increased haemolysis, and multi-organ damage. Although severity and frequency of VOC varies, VOC is considered implicated in irreversible organ damage and shortened life expectancy in SCD patients.

Hypoxia, pro-inflammatory changes, and pro-thrombotic changes are known to be causative in VOC. However, since neither biomarkers for VOC diagnosis nor pre-clinical models mimicking VOCs are well-established, VOC biology is incompletely understood. Genetically engineered mice expressing human sickle haemoglobin develop patient-relevant phenotypes, but VOCs are not generally observed. Published studies using e.g. proinflammatory agents or physiological stress such as hypoxia have demonstrated induction of symptoms similar to human VOC in SCD mice. However, these studies typically focus on only one endpoint and/or provide few details on experimental conditions, and the extent to which induced crisis in mouse models replicates human pathophysiology has not been addressed systematically. The objectives of this project are to use anaesthetised SCD mice in establishment and validation of methodology to induce a condition as similar to human VOC as possible, and application of the model in studies of VOC biology, identification of biomarkers, as well as investigation of response to different therapeutic principles. Both therapeutic interventions (directly targeting VOC), and preventative interventions (targeting the root cause of SCD) will be applied.

Planned methodologies in the project include in vivo studies in mice, histology, and whole blood measurements using automated analysers and FACS. Live observation of blood flow during VOC can be accomplished using an intravital microscopy setup. Technologies such as cytokine screens, qPCR, microarray and/or NGS can be used in identification of new potential biomarkers.

The main outcomes of the project will be to increase the value of an existing mouse model of SCD by proposal of a well-characterised experimental protocol under anaesthesia, study of known therapeutic interventions and potential biomarkers, as well as proposal and preclinical validation of novel VOC biomarkers.

Principal supervisor
Professor Søren Skov
E-mail: sosk@sund.ku.dk

Direct Phone: (+45) 35 33 31 26
Faculty of Health and Medical Sciences
University of Copenhagen

Co-supervisors

Name: Dr. Carsten Dan Ley, Rare Blood Disorders, Novo Nordisk A/S

Email: csdl@novonordisk.com

Name: Dr. Andreas Glenthøj, Danish Center for Hemoglobinopathies, Rigshospitalet

E-mail: andreas.glenthoej@regionh.dk

Name: Dr. Laurent Pierre Burnier, Translational Science, Novo Nordisk A/S

E-mail: lpib@novonordisk.com

Required qualifications

  • MSc in a biological or biomedical science, veterinary medicine, medicine, or other equivalent degree
  • A special interest and competencies in animal models and in vivo pharmacology
  • Function A/B/D (FELASA Category C) course in carrying out animal experiments
  • Curiosity and interest in translational science
  • Biochemical and molecular biology laboratory competencies
  • High level of motivation, responsibility and flexibility
  • Highly enthusiastic, ambitious and team-oriented personality
  • Excellent communication skills in English (written and oral)
Preferred qualifications

  • Previous experience within in vivo pharmacology and animal research, and experience handling laboratory animals
  • Knowledge of biomarker identification / screening and related techniques
  • Insight, experience and/or special interest in benign haematology
General Job description

Your key tasks as a PhD fellow at SUND are to:

  • Manage, carry through and conclude on your research projects
  • Actively participate in PhD courses
  • Write scientific articles and finalise your PhD thesis
  • Participate in international congresses
  • Conduct a research stay at an institution abroad
  • Teach and disseminate your research
We offer

  • The opportunity to work in a state-of-the-art, highly innovative and scientifically stimulating environment with ambitious colleagues
  • Excellent training opportunities, both personally and professionally
  • The opportunity to contribute with new knowledge to an exciting and fast-moving scientific field
Key criteria for the assessment of candidates

  • The grade point average achieved in relevant University degrees
  • Professional qualifications relevant to the PhD programme
  • Relevant work experience
  • Previous publications
  • Other professional activities
  • Language skills
The successful candidate is also required to be resourceful and to possess good interpersonal skills.

Formal requirements

The position is available for a 3-year period for applicants holding a relevant master´s degree.

It is a prerequisite that the PhD candidate is enrolled as a PhD student at the Faculty of Health and Medical Sciences, University of Copenhagen according to the rules stipulated in "Bekendtgørelse nr. 18 af 14. januar 2008 om ph.d.-graden."

Terms of employment
Salary and other terms and conditions of appointment are set in accordance with the Agreement between the Ministry of Finance and AC (Danish Confederation of Professional Associations) or other relevant professional organisations. The position is covered by the Job Structure for Academic Staff at Universities (2020).

Questions
For further information contact Søren Skov, e-mail: sosk@sund.ku.dk

Foreign applicants may find the following links useful: www.ism.ku.dk (International Staff Mobility) and www.workingconditions.ku.dk

Application Procedure
Applications - in English - must include:

  • Cover Letter, stating for which PhD project you are applying and detailing your motivation and background for applying for the specific PhD project
  • CV
  • Diploma and detailed transcripts of records
  • Other information for consideration, e.g. list of publications (if any), peer reviewed and other
  • Personal recommendations
  • A maximum of 3 relevant scientific works which the applicant wishes to have included in the assessment
The application will be assessed according to the Ministerial Order no. 242 of 13 March 2012 on the Appointment of Academic Staff at Universities.

The University of Copenhagen encourages all interested in this post to apply.

After the expiry of the deadline for applications, the authorized recruitment manager selects applicants for assessment on the advice of the Appointment Committee. All applicants are then immediately notified whether their application has been passed for assessment by an expert assessment committee. Selected applicants are notified of the composition of the committee and each applicant has the opportunity to comment on the part of the assessment that relates to the applicant him/herself. You can read about the recruitment process at http://employment.ku.dk

Please submit the application with the required attachments by clicking on "Apply online". Only online applications will be accepted.

The application deadline is 29 November 2020, 23.59 p.m.

Interviews are expected to be held in week 1 and 2 (2021)


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