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 titleType of researchSupervisor(s)
Literature survey on how distinct dietary fibres can affect microbiome compositionLiterature thesis (Bachelor or Master)Prof, Remco Kort (r.kort@vu.nl)
KeepFoodSimple ( https://keepfoodsimple.nl) is looking for a student Food Science or related fields of study who is interested in an internship studying the relation between type or chemical structure of food fibre and its effect on the composition of the microbioom. A further questions is: what is the effect of combinations of different types of fibre on the composition of the microbioom. Fibre in this context is defined as non-digestible oligo- and poly saccharides. This study will also include an evaluation of the various methods to establish microbioom composition. If possible this study will be linked to ongoing experiments on the relation between fibre type and microbioom composition.
This internship will be guided by prof. dr. Remco Kort, Microbiology, Free University Amsterdam and Fons Voragen Em. prof. of Food Chemistry, Wageningen University & Research. Start coming months.
KFS will pay a compensation of 250€ per month.
Literature survey on how distinct dietary fibres can affect microbiome composition
It is well known that dietary fibers have a positive effect on gut and metabolic health. They slow down gastric emptying and reduce sugar response after eating.
They thicken the contents of the intestinal tract, causing a better stool consistency which help removing potentially toxic metabolites from the colon.
The fibers are also important substrates for a wide range of gut bacteria. These bacteria produce various short chain fatty acids that strengthen the gut membrane, stimulate immune response and affect lipid, glucose and cholesterol metabolism in various tissues. Regular high consumption of dietary fibers result in a very diverse microbiome and it suppresses pathogenic bacteria that excrete carcinogenic metabolites.
These insights have led to a general recommendation to consume at least 30 to 40 grams of dietary fibers per day. However, food scientist and dieticians have not yet specified what particular type of fibre and what mix has the most beneficial health effect.
Various studies have shown that different types of fibers stimulate different groups of bacteria, leading to different metabolic effects. Arabinoxylans, for instance, stimulate growth of the bacterial genera Bifidobacterium and Akkermansia. This is much less so with inulin. Different types of pectins have different physiological effects. Rhamnogalacturonan 1 is well noted for its immune stimulating effects.
The objective of this study is to make a comprehensive survey on how all the major dietary fibers present in grains, beets & carrots, fruits, nuts, beans and vegetables affect microbiome composition and the resulting physiological and metabolic effects.
Please contact Remco Kort in case of any interest
Understanding optimal resource allocation strategies in yeastsComputational
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
Measuring glucose and fructose 1,6-bisphosphate metabolism in single yeast cellsExperimental (Bachelor or Master)Dennis Botman
d.botman@vu.nl
Glucose is the major carbon source for Saccharomyces cerevisiae to grow on. It is metabolized using glycolysis, in which the intermediate fructose 1,6-bisphosphate is a key metabolite which seem to control the flux of glycolysis. Therefore, we need robust glucose and fructose 1,6-bisphosphate biosensors to measure its levels inside cells. This will help to elucidate how cells coordinate their carbohydrate metabolism at a single-cell level. In this internship, you will develop and characterize biosensors for these 2 important metabolites.
Using CRISPR/CAS to create mutant yeast strainsExperimental (Bachelor or Master)Dennis Botman
d.botman@vu.nl
In the lab, mutants strains of micro organisms are used routinely to explore and elucidate cellular physiology. This also holds for yeast, where mutants are often created by using so-called auxotrophic markers. These markers are metabolic genes that are deleted and can be restored again by replacing the studied gene of interest for the auxotrophic marker. Auxotrophic markers themselves can already affect cellular physiology, thereby making this technique debatable. In order to make clean mutant strains, we want to set up and use CRISPR/CAS to make gene knockouts without using any markers (scarless). In this internship, you will use CRISPR/CAS to knock out specific genes important in our research in a fully WT strain without any auxotrophic markers (scarless). You will also perform whole genome sequencing and characterization of the mutant strains.
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

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