About the project
MIRACLE: is a Marie Sklodowska-Curie Action Doctoral Network:

Mobility requirements: Candidates must not have resided or carried out their main activity in the Netherlands for more than 12 months in the 36 months immediately before their recruitment date. This information will determine whether you fulfil the EU mobility rule for the position. See MIRACLE website for more information.

What will you be researching?
Amsterdam University Medical Center in Amsterdam is looking for a PhD student/Doctoral Candidate (DC).

In general, disease phenotypes of individuals, also in the context of individual cells, are driven by environmental context and molecular makeup, such as genetic, epigenetic, and metabolic status. A broad range of available datasets, including, but not restricted to, UK-Biobank and FinnGen, will be studied, focusing in particular on Cardio Metabolic Disease (CMD) subpopulations. This DC (DC8) will study and implement the integrations of distinct layers of -omics data to identify novel molecular targets that impact inflammation, which may be amenable for diagnostics or treatments.

This DC position is part of the MIRACLE consortium, a Marie-Sklodowska Curie Actions Doctoral Network that started on the 1st of February 2024.

About the role
The PhD student will be enrolled in the Amsterdam UMC Doctoral School.

• This PhD student will work on the identification of new targets that may contribute to the modulation of inflammatory macrophage activation in atherosclerosis by performing integrative multi-omics, machine-learning-driven analyses. These analyses will be based on existing data sets, and where possible, newly generated ones. Data repositories, including, but not restricted to, the UK Biobank and FinnGen, will be assessed, focusing on CMD subpopulations.
• The fellow will collaborate with other DCs to set up additional translational tests to validate top candidates using in vitro screening systems for functional consequences on macrophage activation through pharmacological (drugs) or genetic (CRISPR) interventions.
• Ultimately, validation experiments will be conducted to advance the therapeutic targets in in vivo models for atherosclerosis.

COLLABORATORS AND SECONDMENTS IN THIS PHD PROJECT

University of Eastern Finland
As part of this project, the PhD student will visit the A.I. Virtanen Institute for three months. The institute is a part of the University of Eastern Finland Faculty of Health Sciences, and the visit will be supervised by Dr. Minna Kaikkonen.

The A.I. Virtanen Institute is a modern facility for basic and translational molecular medicine with 250 researchers and other personnel. It is well-equipped for all molecular laboratory work, cell biology, advanced imaging, genetics, and multi-omics research.

Profile
REQUIRED EDUCATION LEVEL: A degree (MSc, or equivalent) in Health or Life Sciences (Bioinformatics, Molecular Biology, Immunology, Genetic Epidemiolgy). Candidates in the final stages of obtaining their degree are eligible to apply.

REQUIRED LANGUAGES: ENGLISH: Excellent, both written and spoken.

SKILLS/QUALIFICATIONS:

• We expect a Master´s degree (or equivalent) in Health and/or Life Sciences, with provable skills in Bioinformatics (R, Python, Slurm, Snakemake/Nextflow).
• Furthermore, the applicant should be able to perform team-oriented as well as independent work.
• Additional desirable methodological skills: excellent background in two or more of the following: Genetic/Molecular epidemiology, molecular biology, biochemistry, cell biology, immunology and/or microbiology, hands-on knowledge of analytical methods (single cell and/or spatial Molecular analyses).

Our offer

• An inclusive work environment.
• Access to state-of-the-art training within the MIRACLE doctoral network, at an academic, policy and industry level.
• Opportunities to collaborate with discipline specific world leading researchers.

Salary and conditions

• As a MSCA DN doctoral candidate, you will receive a gross pre-tax salary of € 2901,- per month (which will increase to €3359 in year 2, €3514 in year 3 and €3677 in year 4).
• As is normal in a Dutch PhD contract at Amsterdam UMC, you will enter an employment agreement for the duration of the PhD trajectory, which means 4 years fulltime (36 h/w). The compensation that Amsterdam UMC receives from the EU covers 3 years, so Amsterdam UMC offers an extra year of employment (including education and income) compared to the usual MSCA DN trajectories.

For early-stage Marie Sklodowska-Curie fellows in the Netherlands, the level of the living allowance plus mobility allowance is typically equal to or slightly lower than the obligatory minimum salary level for PhDs according to Dutch law. In the first year of employment the salary for PhD students in the Netherlands is lower than the amount of the Marie Sklodowska-Curie living allowance plus mobility allowance, but it is higher in the following years. So, over the first three years, at least the total of the Marie Sklodowska-Curie fellowship will be paid to the researcher. The family allowance is also included in the PhD salary (if the fellow is entitled to this family allowance). If after 3 years a calculation shows that you didn’t receive the total amount of allowances you were entitled to, you will receive an extra payment to cover the difference.

The period of employment for this PhD is four years. Appointment to the PhD programme implies that you will be admitted to the Amsterdam UMC Doctoral School within three months of employment, and that you will participate in a structured PhD programme during the employment period.

The prerequisite is that you are present and accessible at the university on a daily basis.

RENUMERATION: The per annum MSCA PhD student living and mobility allowance (plus family allowance if applicable, family status is assessed at recruitment) is in line with EU-MSCA requirements. This amount will be subject to tax and employee’s National insurance deductions and will be paid in EURO. Details regarding the financial aspects of a Marie Sklodowska-Curie fellowship in the Netherlands can be found here.

About the workplace
The Amsterdam University Medical Center (Amsterdam UMC) is one of the foremost research institutes in the Netherlands, as well as one of its largest hospitals. Over 7,000 people work here to provide integrated patient care, fundamental and clinical scientific research, and teaching. The department of Human Genetics participates in the MIRACLE network together with the department of Medical Biochemistry where one additional Doctoral Candidate (DC6) will be hosted.

The integrative modelling research in the DC8 position will be performed in collaboration between these MIRACLE departments and is particularly focused on the detection of molecular mechanism that play a role in macrophage activation in the context of atherosclerosis, also known as a low-grade inflammatory disorder. The primary hosting for DC8 will be at the Amsterdam UMV, Department of Human Genetics, Section of Epigenetics.

Dr. Peter Henneman, Dr. Koen Prange and Prof.dr. Menno de Winther will be supervising the DC8 project at Amsterdam UMC. About the supervisors:

• Dr. Peter Henneman is affiliated with the Department of Human Genetics, heading the Epigenetics section. This section holds a strong track record in the discovery of novel epigenetic signatures of rare Mendelian disorders (EpiSign) and translation studies thereof. In addition, Dr. Henneman is affiliated to the Core Facility Genomics embedded in the department of Human Genetics, Genome Diagnostic Laboratory.
• Dr. Koen Prange is an expert in bioinformatics and epigenetic regulation of gene responses with experience in scRNAseq and extensive genomic analysis.
• Prof.dr. Menno de Winther heads the Experimental Vascular Biology group, has a long experience in macrophage regulation in CVD and is the current director of the research institute Amsterdam Cardiovascular Sciences (ACS).

The MIRACLE network, funded by the European Commission (2024-2028), is made up to train a new generation of researchers working on the latest advances in single cell biology, multi-omics analysis and newest insights in macrophage biology in the context of cardiometabolic disease. These advances revealed heterogeneous and dynamic accumulation of (immune) cell populations in tissues that associate with disease initiation, development and particularly clinical outcome, a notion that has immense implications on our view of chronic inflammatory diseases and their treatment. Unique know-how is ready to be transferred to highly talented research fellows.

In MIRACLE, twelve doctoral candidates will receive tailored training that enables them to study local and environmental factors that drive cardiometabolic inflammation as well as develop strategies to suppress them, via the integrated use of cutting-edge single cell, spatial mapping, …