DC8

Project: implementing multi-omic approaches to identify causal genes in inflammation

PhD position at Amsterdam University Medical Center

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. 

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: 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.
• Nanostring: Another part of this PhD project consists of a secondment period of two months at NanoString's headquarters and training facility in Amsterdam, The Netherlands. NanoString enables scientists worldwide to visualize molecular interactions in three dimensions using three different systems: the nCounter® Analysis System, the GeoMx® Digital Spatial Profiler (DSP), and the CosMx™ Spatial Molecular Imager (SMI) platform. As a result, scientists can observe the multi-omic expression of genes and proteins in the natural context of tissue structure.

ABOUT AMSTERDAM UNIVERSITY MEDICAL CENTER, LOCATION AMC/VUMC 

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. 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. Prange is an expert in bioinformatics and epigenetic regulation of gene responses with experience in scRNAseq and extensive genomic analysis. Prof.dr. 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).