Cell Physiology and Applications
Below, you can find the updated list of Bachelor and Master internships available at the moment.
For more information on available internships on Single-cell Physiology and on Host microbiome interactions, please contact directly the teamleaders in this group:
Jurgen Haanstra – j.r.haanstra[at]vu[dot]nl
Herwig Bachmann – h.bachmann@vu.nl
Remco Kort – r.kort@vu.nl
| Project title | Type of research | Supervisor(s) |
|---|---|---|
| 1. Accessory functions in the pangenome of the human vaginal commensal Lactobacillus crispatus 2. Bacterial strain engraftment in the gorilla gut microbiome after fecal transplantation | Two Internships Bioinformatics (Master) | Dr Douwe Molenaar Prof, Remco Kort (r.kort@vu.nl) |
| 1. The accessory genome in bacteria can be considered the cradle for adaptive evolution. For this internship a set of whole genome sequences of L. crispatus will be analyzed and accessory functions in the pangenome will be evaluated with a particular emphasis on functions that are important for sustained colonization in the host. Techniques: differential analysis of a large set of sequenced genomes. Duration: 6 months Further reading: van der Veer C, Hertzberger RY, Bruisten SM, Tytgat HLP, Swanenburg J, de Kat Angelino-Bart A, Schuren F, Molenaar D, Reid G, de Vries H, Kort R. (2019) Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: implications for in vivo dominance of the vaginal microbiota. Microbiome 7:49. Hertzberger R, May A, Kramer G, van Vondelen I, Molenaar D, Kort R (2022) Genetic elements orchestrating Lactobacillus crispatus glycogen metabolism in the vagina. Int J Mol Sci. 23:5590. 2. A fecal transplantation has been carried out to cure Akili, the ARTIS silverback gorilla, by recovery of the gut microbiota after antibiotic treatment. Longitudinal 16S rRNA profiling and metagenome data have been collected in donor and recipient feces to monitor bacterial population dynamics in the gut before, during and after the fecal transplantation intervention. The data will be analyzed with particular emphasis on bacterial strain engraftment. techniques: comparative metagenome analysis (optional metabolic analysis) duration: 4-6 months Further reading: Houtkamp IM, van Zijll Langhout M, Bessem M, Pirovano W, Kort R. (2023) Multiomics characterisation of the zoo-housed gorilla gut microbiome reveals bacterial community compositions shifts, fungal cellulose-degrading, and archaeal methanogenic activity. Gut Microbiome. 4:e12 |
||
| Understanding optimal resource allocation strategies in yeasts | Computational Bachelor (with strong interest in computational methods)/Master | Pranas Grigaitis (p.grigaitis@vu.nl) |
| Filled till Summer 2024 Optimal allocation of limited resources, such as nutrients, energy, or physical volume of the cell enables to sustain cell maintenance and growth of cells, and is critical for unicellular microorganisms to strive. Moreover, the optimal allocation pattern can be context-specific, heavily depending on the environment the microorganisms live in. Therefore, computational techniques are of great help in order to capture and analyse resource allocation strategies/patterns, preferably at genome-scale. Thus in this topic, we blend existing knowledge of biochemistry and microbial physiology together with different types of computational modelling to advance the understanding of the organization of metabolism of two major eukaryal model organisms: budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. Techniques: genome-scale metabolic modelling (both conventional and proteome-constrained) (PySCes CBMpy, COBRA etc.), kinetic modelling (COPASI), programming with Python and/or R for data analysis and visualization |
||
| Metabolism in health and disease | Experimental or computational (combinations are possible) Bachelor/master | Jurgen Haanstra |
| The work in this topic aims to understanding control and regulation of metabolism to reveal selective drug targets in pathogens and other disease-causing cells. In addition, we also want to understand these aspects for healthy cells to make sure that interventions against the disease will not harm them. We work with the parasite Trypanosoma brucei and with liver cancer cells in the wetlab, but also do research on the parasite Schistosoma mansoni, on head- and neck cancer and blood cell precursors in the dry-lab (always in collaboration with experimental labs Techniques: Wetlab: cell culture, metabolite measurements, enzyme assays. Dry lab: kinetic modelling (COPASI, PySCes (python-based), genome-scale modelling |
||
| Developing a new fluorescent glucose biosensor | Experimental (Bachelor or Master) | Dennis Botman d.botman@vu.nl |
| Glucose is the major carbon source for Saccharomyces cerevisiae to grow on. In order to measure glucose levels in single living yeast cells, biosensors based on fluorescent protein are needed. Currently, none of the fluorescent biosensors for glucose are suitable as they are dim or pH-sensitive. We have developed 2 new glucose biosensors based on a cyan fluorescent protein and further development and characterization is needed. Once these sensors prove to be robust tools to measure intracellular glucose levels, we will use it to elucidate glucose metabolism in budding yeast. | ||
| Kinetic modelling to understand the link between NAD+ metabolism and oxidative stress. | Theoretical (Master) | Daniëlle Gramsbergen d.s.gramsbergen[at]vu[dot]nl Personal page |
| What you will be working on and the core skills you will learn. In this ongoing project, we are systematically building a kinetic model to better understand the link between NAD+ metabolism, central energy metabolism and oxidative stress in human liver cells. An existing model describes biosynthesis and consumption pathways of NAD+, but still lack details of central energy metabolism (glycolysis and respiration). We are looking for a motivated student to work on and expand the current model with kinetic descriptions of central energy metabolism. You will learn how to translate biological knowledge to ordinary differential equations, how to code such a model in Mathematica and which questions kinetic models of metabolism allow us to answer. Why this work is relevant. Oxidative stress is defined as an overabundance of reactive oxygen species (ROS) and is associated with a decline in concentration of this abundant and important redox cofactor: NAD+. How this NAD+ decrease manifests on a biochemical level and how the NAD+ metabolome is influenced by oxidative stress is largely unknown. However, because oxidative stress is linked to ageing, neurodegenerative disease, viral infection and many more pathologies, gaining an understanding of the interplay between oxidative stress and the NAD+ metabolome on a biochemical level is the first step in designing novel strategies to combat oxidative stress in humans. Because the total poolsize of NAD+ is mostly dependent on the balance of biosynthesis and consumption of NAD+, these were the first pathways included in the model and already gave us some insight on potential strategies to perturb this NAD+ metabolome to reduce oxidative stress. However, because NAD+ is also an important redox factor in central carbon and energy metabolism, we would like to find out using kinetic modelling how changes in energy metabolism during oxidative stress influences these biosynthesis and consumption pathways. |
||
| Exploration of the nutritional status on metabolic robustness in Caenorhabditis elegans | Experimental (Master) | Johan van Heerden j.van.heerden[at]vu[dot]nl Personal page and Samantha Hughes (Toxicology) s.hughes[at]vu[dot].nl |
| Background: There is a close interaction between oxidative stress, immune activation, energy metabolism and cell viability. There is also growing awareness that oxidative stress plays a key role in the aging process as well as diseases including Parkinson’s Disease, cancer, diabetes, and chronic inflammation. To mitigate oxidative stress, cells rely on various detoxification and repair processes. These processes, in turn, are critically dependent on NAD+, a molecule that functions as a coenzyme in cellular redox reactions, and as a substrate for stress response and repair pathways. Ensuring a sufficient supply of NAD+ is therefore a key determinant of cellular robustness against oxidative stress. Not surprisingly then, diseases associated with oxidative stress are also often characterized by decreased levels of NAD+. Nutritional status of the cell can influence NAD+ levels and it is possible that this confers some protection against oxidative stress. To be able to test this hypothesis, it is important to have a clearly defined culture medium and methods to quantify oxidative stress. To this end, the nematode Caenorhabditis elegans is an ideal model. The nematodes can be cultured in a chemically defined culture media and are well characterized in terms of life-history traits (e.g., brood size, growth, lifespan). In addition, the use of fluorescent reporters allows for a quick readout of the level and impact of oxidative stress. What you will learn: During this project you will become familiar with the handling of C. elegans and how to measure standard endpoints of viability including brood size, growth and lifespan. You will learn to use an inverted fluorescent microscope to observe the fluorescent reporters as well as working with a variety of image processing tools, such as ImageJ. Planned activities: • Define the axenic growth media (without bacterial food source) and set up an SOP • Generate a dose-response curve for H2O2 (to induce oxidative stress) for viability, growth and fertility • Characterise the effect of the induction of oxidative stress using translational reporters for ROS • Link the level of oxidative stress to changes in NAD+ metabolism using mutants and reporter strains Supervisors: Dr. Samantha Hughes Dr. Johan van Heerden |
||
Recent Comments