Living cells are complex. The average human body consists of approximately 37 trillion cells each containing thousands of molecules that work together to enable the cell to carry out its specific function. In this project, you will specifically look at immune cells, the key players of our defense system.

The DICE database (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) provides a high quality dataset with gene expression and eQTLs for 5 different immune-cell types in different activation stages (total of 15 datasets). This data will be used to build and analyze cell-type specific epigenetic regulatory networks.

This project presents an exciting opportunity to discover crucial connections between cardiomyopathies and metabolism that might improve medical treatment options.​

The discovery and functional characterization of novel components of mtDNA maintenance will improve our understanding of these processes in health and disease. Moreover, it will improve genetic diagnostic tests and open possibilities for designing therapeutic interventions, improving quality of life for patients with mitochondrial disorders.

Mitochondrial disorders are the most common inherited metabolic disorders affecting over 1 in 5000 people. Although rapid progress in characterizing the mitochondrial proteome has fueled progress in understanding the role of mitochondria in health and disease, functional information is lacking for half of the proteins in the mitochondrial proteome. Moreover, the mitochondrial proteome is believed to be far from complete. As a result, 40-50% of mitochondrial patients remain genetically undiagnosed.

Mitochondria are dynamic organelles crucial for cellular energy production. Their dynamic nature enables them to adapt their morphology to the physiological needs of the cell, through the process of fusion and fission, collectively referred to as mitochondrial dynamics. Although several mitochondrial dynamics proteins have been identified, not all involved proteins and mechanisms are known, restricting our understanding of disorders originating from a defect in mitochondrial dynamics. The aim of our research is to identify and functionally characterize novel mitochondrial dynamics proteins.

Through computational approaches based on protein-protein interactions, we identified several novel mitochondrial dynamics candidate proteins. In order to elucidate their exact role in mitochondrial dynamics, we perform functional experiments including gene-specific knockdown, assessment of mitochondrial morphology through fluorescent and electron microscopy, subcellular localization studies, assessment of mitochondrial activity, and many others. Moreover, we generated RNAseq data from cells in which established mitochondria dynamics proteins and novel candidate proteins were knocked down. This data will be used for regulatory network analysis and metabolic modeling to unravel the mechanisms and pathways involved, leading to a better understanding of mitochondrial dynamics in health and disease.

In recent years, advances in non-invasive neuroimaging and genetics have created the possibility to collect large amounts of data in a manageable time period. The question remains whether all this data can help us to elucidate the functioning of the human brain, and to study the influence of genetics on brain processing.

At the Maastricht Centre for Systems Biology (MaCSBio), one of our aims is to achieve new insights into the process of learning. In this project, we will explore correlates of learning and memory performance (as defined on the behavioral data of the HCP) in either the brain data (structural and functional connectivity) or the genetic data (through network and pathway analysis).

Moreover, we aim to explore the correlation between structural/functional brain data and genetics. This is a large project, and the student will be able to choose the main direction of the internship within the project based on his/her interest. The ultimate goal of the project is to connect processes functioning at the small spatial scale of molecular pathways to the large spatial scales of interacting neuronal populations. The earliest possible starting date of this internship is October 2019.

Hearing, understanding, and interacting with sounds is crucial in our everyday life. While seemingly straightforward, hearing is an extremely adaptive and flexible process. For example, in a noisy environment we can tune in to those sounds that are currently important to us, and we can learn to recognize the voice of a new friend. Recent invasive studies showed that this flexibility is accompanied by rapid and/or long-lasting changes in brain processing.

Various studies are planned in this direction, and the exact content/focus of the project will be determined together with the student. The earliest possible starting date of this internship is October 2019.