PhD students for SYMPHONY project

NWO-Nationale Wetenschapsagenda grant 2018-2019

36 hours per week

Job description

The aim of the project “SYMPHONY: Orchestrating personalized treatment for patients with bleeding disorders” is to establish best treatment choice for each individual with a bleeding disorder based on bleeding tendency. This will be achieved by improving current diagnostic tests to measure hemostatic potential and by performing fundamental research into the pathophysiology behind interindividual differences in bleeding phenotype and treatment response, using novel techniques such as proteomics, and both IPSc and endothelial cellular systems.

This will be achieved by intensive collaborations between the twelve workpackages (WP) (14 fte PhD and 1 fte postdoc), spread over three themes: Diagnostics, Treatment and Fundamental research. Clinical research will focus on among others: a) Treatment optimization by personalization, increasing quality of care at acceptable costs; b) Guidance of complex clinical shared decision making for novel therapeutic options; c) Patient-orchestrated implementation of health care innovations using e-health modules. The SYMPHONY consortium is a broad interdisciplinary cooperation consisting of diverse disciplines: (pediatric) hematology, vascular medicine, clinical genetics, clinical pharmacology, psychology, ethics, epidemiology & methodology, mathematics, health care economics, information & data technology, biochemistry, molecular biology, molecular genetics and cell biology, laboratory medicine, business economics, marketing, sales & patient advocacy.

For this project a total of 14 PhD’s and one Post-doc will be hired.

CLOSING DATE: 17th OF JANUARY 2020

Current hemostasis laboratories diagnose patients using tests based on coagulation factor levels. These are however not sensitive enough to predict inter-individual heterogeneity in bleeding phenotype. Therefore, there is a need to develop novel tests for more precise diagnosis of bleeding disorders as well as to better monitor treatment. A novel diagnostic assay should: a) reflect clinical bleeding phenotype; b) predict bleeding risk; and c) monitor treatment in patients on prophylaxis, in the perioperative setting and during acute bleeding events. In this project, we aim to develop reliable tests that measures hemostatic potential.

To achieve this we will:
• Develop novel assays & improve current research assays to quantify hemostatic potential.
• Combine diagnostic tests to create a hemostatic profile for each individual patient.
• Validate optimized diagnostic approaches by correlating clinical characteristics with test results in specific patient populations.

Qualifications and skills:
For this PhD project we search for a motivated researcher who has recently graduated as a biomedical scientist, biochemist or medical biologist. You are a good collaborator with interest in biochemical techniques and laboratory diagnostics. You find it a challenge to use the newest biochemical techniques in developing novel diagnostic tools.

Start date: 01 Februari 2020

Institute: Erasmus MC

Supervisor: Prof. dr. M. de Maat

Terms of Employment:
You will receive a temporary position for 1 year. If suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

CLOSING DATE 17th OF JANUARY 2020

Platelet disorders are amongst the most common causes of excessive blood loss, but are difficult to diagnose. Using a multidisciplinary and fully translational approach, we aim to improve diagnostics for patients with these disorders. In a nationwide collaborative study, you will apply newly developed state-of-the-art diagnostic tests for analysis of platelet function in patients with a suspected platelet function disorder. In addition, you will investigate genotype-phenotype associations to elucidate molecular mechanisms responsible for platelet function disorders.

Qualifications and skills:
MSc in (Bio)medical Sciences or Biology with experience in cell biology and biochemistry, who is passionate about thrombosis and haemostasis.

Start date: 01 February 2020

Institute: UMC Utrecht

Supervisor: Prof. dr. R. Schutgens

Terms of Employment:
You will receive a temporary position for 1 year. If suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

CLOSING DATE 17th OF JANUARY 2020

Implementation of value-based health care into the field of bleeding disorders is vital to balance both patient- and doctor reported health care outcomes with costs of treatment, especially in the light of emerging even more expensive therapeutic agents.

To achieve this we will:
• Establish a core set of patient, care provider-reported outcomes according to value based health care methodology
• Develop valid, reliable, responsive, user-friendly instruments to measure the core outcomes set.
• Investigate the organizational impact of a value-based health care approach on a health care domain, that is characterized by a high financial burden of treatment products in relation to other health care activities.

Qualifications and skills:
Enthusiastic and ambitious PhD candidate with aspirations to perform high quality research and to implement medical innovations. Excellent communicative and organizational skills are of high priority. The research project should result in a PhD thesis.

Start date: 1 April 2020

Institute: Erasmus MC

Supervisor(s): Prof. dr. J. Hazelzet

Terms of Employment:
You will receive a temporary position for 1 year. If the suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

CLOSING DATE 17th OF JANUARY 2020

Population PK and PK-PD models will be developed for clotting factors concentrates (factor VIII, factor IX, von Willebrand factor) and desmopressin, which are administered in hemophilia and von Willebrand disease. Routine retrospective and prospective clinical data will be obtained from different treatment centers and will be analyzed using non-linear mixed effects modelling (NONMEM). The developed models will be applied in unique prospective multicenter trials in which doses are individualized and predicted on basis of individual patient PK using Bayesian statistical techniques. Thus optimizing treatment to improve quality of care in the light of both current and novel therapeutic options (standard half-life concentrates, extended half-life concentrates) and to implement personalized treatment of replacement therapy and desmopressin in a patient and treater-friendly manner for all patients with a bleeding disorder long term.

Qualifications and skills (3 fte):
– Educational background in biopharmaceutics, pharmaceutical sciences, pharmacometrics, mathematics, statistics/biostatistics , computational biology/chemistry
– Proficiency in NONMEM, R or other similar programing language
– Population PK / PKPD analyses
– Strong skills in mathematical problem solving, critical data analysis/interpretation, and statistics.
– Scientific understanding of pharmacological properties

Start date: 1 March 2020 – 1 Januari 2021

Institute: AMC

Supervisor(s): Prof. dr. R. Mathôt

Qualifications and skills (3 fte):
Enthusiastic and ambitious PhD candidate with medical background and aspirations to perform high quality research and to implement medical innovations. Excellent communicative and organizational skills are of high priority. The research project should result in a PhD thesis.

Start date: 1 April 2020 – 1 Januari 2021

Institute: Erasmus MC

Supervisor(s): Dr. M.H. Cnossen

Terms of Employment:
You will receive a temporary position for 1 year. If the suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

CLOSING DATE 17th OF JANUARY 2020

Health care for persons with inborn bleeding disorders is organized in comprehensive multidisciplinary care teams, including psychosocial support with a strong emphasis on self-management; e.g. severely affected patients are trained to self-infuse clotting factor concentrate at home. In this project, you will further improve patient empowerment by developing shared decision making strategies and establishing a digital personal health record where patients can share their health data with care providers.
In current era of innovative treatments including designer drugs and gene therapy, treatment choice  is rapidly expanding. You will develop a machine learning decision support system to get the right treatment to the right patient at the right time. With these novel e-health tools we aim to prioritize implementation of personalized care strategies and value based health care principles developed in the other projects of the consortium.

Qualifications and skills:
Enthusiastic and ambitious PhD candidate with medical background and aspirations to perform high quality research and to implement medical innovations. Excellent communicative and organizational skills are of high priority. The research project should result in a PhD thesis.

Start date: 1 February 2020

Institute: AMC

Supervisor(s): Dr. S. Gouw

Terms of Employment:
You will receive a temporary position for 1 year. If the suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

CLOSING DATE 17th OF JANUARY 2020

Calculate costs and cost effectiveness of treatment for standard and novel emerging treatment modalities. Innovative quasi-experimental designs will be used to study the effectiveness of the newer treatment options available for patients with bleeding disorders. Uniquely, empirical data collection will be combined with a decision analytic modelling approach to obtain – model based – estimates of the cost-effectiveness of the joint SYMPHONY interventions.

Qualifications and skills:
Enthusiastic and ambitious PhD candidate with aspirations to perform high quality research and to implement medical innovations. Excellent communicative and organizational skills are of high priority. The research project should result in a PhD thesis.

Start date: 1 October 2020

Institute: Erasmus MC

Supervisor(s): Dr. H. Lingsma

Terms of Employment:
You will receive a temporary position for 1 year. If the suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO) based on a full time position. The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

The objective of this project is to ethically evaluate gene therapy and other novel interventions for patients with bleeding disorders. Special attention will be given to ethical questions regarding access to treatment, distributive justice, and other research ethics challenges regarding biomedical innovations. Background: Previous consultation of stakeholders by the World Federation of Haemophilia [1] and Dutch experience with gene therapy and Emicizumab (one of the novel therapies) have identified a number of ethical aspects of these treatments, including uncertainty about long term risks, patient-identity and what counts as a decent minimum in health care (one time high costs of gene therapy versus continuing costs of other interventions). These issues should be clarified before novel therapies can become part of the standard of care.

Qualifications and skills:
The PhD candidate is required to have an (almost) finished master’s degree in Medicine, Biomedical sciences, Philosophy, Law, Theology or Health sciences. A master’s degree in Applied Ethics or experience with Medical Ethics would be an asset.
We are looking for a candidate with good social and communicative skills, who is ambitious and pro-active, and who can work independently.

Start date: 1 October 2020

Institute: PhD will be primarily based at UMC Utrecht, part of the work will be done in UMCG

Supervisor(s): Dr. R. van der Graaf, Prof. A.L. Bredenoord (both from the Department of Medical Humanities, UMC Utrecht) and Prof. dr. K. Meijer (Department of Hematology, UMCG)

Terms of Employment:
You will receive a temporary position for 1 year. If the suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO) based on a full time position. The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

You will join the proteomics team at Sanquin Research that is part of the Department of Molecular and Cellular Hemostasis, where a vibrant international group of 35-40 colleagues (principle Investigators, postdocs, PhD students and technicians) is dissecting hemostatic networks using mass spectrometry (MS)-based technologies. We aim to gain insight in critical interactions that underlie the interplay between plasma proteins, circulating blood cells and the vasculature. In this project, you will link plasma and blood cell profiles to bleeding phenotype in the two most common inherited bleeding disorders Hemophilia A (HA) & Von Willebrand Disease (VWD). To achieve this goal, you will develop and employ MS-based approaches to (i) Identify novel hemostatic modifiers that explain inter-individual variation of bleeding phenotype in HA and VWD patients (ii) Analyze association of desmopressin-treatment responses with plasma protein profiles (iii) Assess levels of endogenous and exogenous coagulation factor VIII during combined desmopressin/factor VIII concentrate treatment.

The objective of this project is to ethically evaluate gene therapy and other novel interventions for patients with bleeding disorders. Special attention will be given to ethical questions regarding access to treatment, distributive justice, and other research ethics challenges regarding biomedical innovations. Background: Previous consultation of stakeholders by the World Federation of Haemophilia [1] and Dutch experience with gene therapy and Emicizumab (one of the novel therapies) have identified a number of ethical aspects of these treatments, including uncertainty about long term risks, patient-identity and what counts as a decent minimum in health care (one time high costs of gene therapy versus continuing costs of other interventions). These issues should be clarified before novel therapies can become part of the standard of care.

Qualifications and skills:
We are looking for highly motivated candidate with: (i) A master’s degree in chemistry, biology, (bio)molecular/biomedical/pharmaceutical sciences or equivalent (ii) A background in mass spectrometry and liquid chromatography, (iii) affinity with quantitative proteomics, data statistics, and bioinformatics.

Start date: 1 February 2020

Institute: Sanquin

Supervisor(s): Prof. dr. S. Meijer

Terms of Employment:
A dynamic position in a unique organization: this is the only place in the world where medical, pharmaceutical and scientific expertise are combined in a single innovative company.
In addition, we offer the following terms of employment:
•             Pay in accordance with the Sanquin Collective Labour Agreement;
•             A 36-hour position with flexible hours;
•             A temporary position for four years;
•             An end-of-year bonus (pro rata in case of part-time or temporary employment);
•             Various opportunities for education and development;
•             201 hours of leave in case of full-time employment (36 hours per week);
•             Modern terms of employment, with the option of selecting your preferred terms.

CLOSING DATE 17th OF JANUARY 2020

You will be based within the iPSC facility in the Department of Hematopoiesis, which harbors several research groups that study hematopoiesis/immunology in health and disease covering most if not all hematopoietic lineages (>60 postdocs, PhD-students, technicians and group leaders). Sanquin provides a lively, internationally oriented, scientific environment with excellent facilities. Within the iPSC facility, we reprogram somatic cells from control, genome edited and patient material using various ways to introduce the reprogramming factors (e.g. episomal, Sendai, lentiviral). We maintain these iPSC lines on various matrices and developed specific protocols to differentiate iPSC to hematopoietic lineages. Within this project we will setup iPSC disease model systems to confirm the causative genetic basis of specific platelet disorders as discovered by other WPs within the consortium. We will employ genome editing to introduce or repair the putative mutations to confirm this causality. Subsequently, we aim to unravel the mechanisms underlying these diseases. A range of standard biochemical assays depending on the mutation(s) identified, coupled with more advanced high throughout techniques (e.g. proteomics, (single cell) RNA-sequencing, ATAC-sequencing) will be employed and integrated to understand the mechanism behind these diseases. Affected pathways will provide novel targets for therapeutic approaches, which will be tested. Data from this project will show if a specific novel mutation is causative, will provide clues or even solve underlying disease mechanism(s) and identifies possible therapeutic targets.

Qualifications and skills:
• Enthusiastic and ambitious PhD candidate.
• MSc degree in Biomedical Sciences, Molecular Sciences or a closely related discipline.
• Solid background in cell biology, excellent laboratory skills and experience with imaging methodologies, tissue culture and molecular biology.

Start date: 1 February 2020

Institute: Sanquin

Supervisor(s): Dr. E. van den Akker

Terms of Employment:
Challenging translational and fundamental research project in a multi-disciplinary and enthusiastic international team within a large Dutch consortium;
•             Temporary position for 4 years
•             Salary and conditions are conform CAO Sanquin;
•             8,33% end-of-year bonus; i.e. a thirteenth month in case of full-year employment;
•             Partial reimbursement of travel costs;
•             Pension plan with Pensioenfonds Zorg & Welzijn (PFZW);
•             At fulltime employment (36 hours) 201 hours of leave per annum.

CLOSING DATE 17th OF JANUARY 2020

This project focuses on the cellular mechanisms behind inter-individual variation in bleeding phenotypes between patients with bleeding disorders. The hypothesis of this study is that genetic variations in secretory pathway components of platelets and endothelial cells are causative for inter-individual variation in bleeding phenotype. This is a collaboration between clinical and fundamental groups at LUMC, ErasmusMC, Sanquin and UMCU within the SYMPHONY consortium. You will generate ex vivo patient-derived cellular model systems, such blood outgrowth endothelial cells and iPSC-derived megakaryocytes to study the secretory mechanisms in individuals with bleeding abnormalities. Using various experimental approaches, including super resolution imaging, TIRF microscopy, proteomic analysis and CRISPR-engineering you will then investigate the cellular bleeding phenotype in molecular detail.

Qualifications and skills:
• Enthousiastic and ambitious PhD candidate.
• MSc degree in Biomedical Sciences, Molecular Sciences or a closely related discipline.
• Solid background in cell biology, excellent laboratory skills and experience with imaging methodologies, tissue culture and molecular biology.

Start date: 1 February 2020

Institute: LUMC

Supervisor(s): Dr. R. Bierings and Prof. Dr. J. Eikenboom

Terms of Employment:
You will receive a temporary position for 1 year. If the suitability is proven, this will be  extended to 3-4 years. The gross monthly salary is € 2422,- in the first year and increases to € 3103,-  in the fourth year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

CLOSING DATE 17th OF JANUARY 2020

Work environment

The SYMPHONY consortium is a collaboration between the Departments of Pediatric Hematology and Hematology of all six Academic Hemophilia Treatment Centers in the Netherlands (Erasmus MC, AMC, UMCU, UMCG, LUMC, Radboudumc), Department of Public Health Erasmus MC, Sanquin Diagnostics & Sanquin Research, Department of Medical Humanities UMCU, three pharmaceutical companies and the Dutch Patient Society (Netherlands Society of Hemophilia Patients; NVHP).
The SYMPHONY consortium has a yearly General Assembly and many multidisciplinary meetings. The PhD will participate depending on the WP in available and required PhD courses and international conferences.

Qualifications and skills

For these PhD projects we are in search of motivated researchers who have recently graduated as either a biomedical scientist, biochemist, medical biologist, medical doctor (WP06) or a closely related discipline. It is preferable if you have experience in biochemical techniques and laboratory diagnostics for WP03. You also should have excellent writing and communication skills in both English and Dutch.
We are looking for enthusiastic candidates with good social and communication skills, who are ambitious and pro-active, and can work independently. A ‘can do’ mentality, analytical mindset and a demonstrable ability to work in a multidisciplinary team.

Being able to present a certificate of good conduct, a valid proof of identity, diploma’s and/ or relevant registration such as BIG/ RGS are conditions for the appointment.

Information

For more information about this position, please contact Dr. Simone Reitsma, project manager SYMPHONY, phone number: 010-7038200 or contact Dr. Marjon H. Cnossen, principal investigator SYMPHONY, phone number: 010-7036691

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Graduated (recently) MSc or MD (required)
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This project has received funding from the Nationale Wetenschapsagenda under grant agreement No 1160.18.038. This website reflects only the authors’ view and the NWA is not responsible for any use that may be made of the information it contains.