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Our group has been very successfully hosting more than 20 master students over the last years with master thesis projects relating mostly to two fields of research: phosphate metabolism and acid-base balance. Our projects range from studies in cell models and animals to experiments in healthy human subjects or working with samples and data collected from patients. To this end we employ a wide range of state-of-the-art techniques and approaches and all projects offer the opportunity to gain insights and experience with these methods. All methods are established in our group.
We continue to offer opportunities for master thesis projects. A selection of possible topics is listed below and will be constantly adapted. If you are interested in physiological mechanisms or translational research and would like to have more information on these projects or additional topics, please contact us.
Age related kidney and bone diseases
Ageing is the time-dependent decay of physiological functions of cells and eventually tissues. The accumulation of misfolding proteins aggregates due to errors in mRNA translation contributes to ageing. Ribosomes play a fundamental role in translation. Rps9 and Mrps5 encode two proteins that constitute ribosomes. Here we will focus on phenotyping kidney and bone ageing in samples from animal models where Rps9 and Mrps5 function has been ablated. We will analyze phosphate handling, accumulation of aggregates in kidney and bone tissues, bone and kidney histomorphometry and kidney function.
Chronic acidosis is frequently associated with protein wasting and disturbances in amino acid metabolism. We will analyze amino acid content of plasma, urine and organs of mice under control diet or during an acid load and examine the expression of enzymes and transporters involved in organ amino acid metabolism and interorgan amino acid fluxes. Metabolic parameters will be studied and biochemical and cellular pathways of several organs involved in amino acid metabolism analyzed.
Chronic kidney disease (CKD) affects approximately 10% of the population worldwide. Alkali therapy via supplementation with sodium bicarbonate has been shown to delay the progression of CKD in humans and rodents with metabolic acidosis. With this project we aim to investigate how alkali therapy affects blood, urine, and renal metabolome in a renal crystallopathy model in mice.
Interplay of endocrine factors in control of renal phosphate excretion
The kidney is the central organ controlling systemic phosphate levels and patients with chronic kidney disease suffer from phosphate overload and the resulting excessive cardiovascular morbidity and mortality. In vitro data suggest that some of the hormones controlling renal phosphate handling strongly interact in renal cells. We will test this by combining in vivo and in vitro experiments using transgenic mice and cell culture to dissect the relevance and signaling of hormones such parathyroid hormone, Fibroblast growth Factor 23, and Heparin-binding Epidermal Growth factor.
The CaSR controls local and systemic calcium metabolism, in part via parathyroid hormone (PTH) and by controlling local transport pathways in many epithelial organs. However, calcium and phosphate metabolism are tightly linked and the CaSR may also sense phosphate. Here, using cell culture and various transgenic mouse models we examine a role of the CaSR in phosphate homeostasis.
The intestine absorbs of many nutrients, among them phosphate. The absorption is mediated by active transcellular phosphate transporters and a yet poorly characterized paracellular pathway. Paracellular ion permeability in many organs is controlled by specific claudins but no claudin for phosphate has been identified. Here we test, whether claudin 3 has a role in intestinal phosphate absorption by using human intestinal cell lines and KO mice for claudin 3 to examine how claudin 3 affects phosphate fluxes and systemic phosphate balance.
Paracellular phosphate absorption proceeds via tight junctions containing various proteins including claudins and is the major pathway of phosphate absorption. The molecules controlling paracellular phosphate absorption remain unknown and we will use here CRISPR/Cas modified cell culture models (to be generated), ex vivo small and large intestines, and functional assays to determine the protein complex regulating paracellular phosphate absorption. Moreover, we will determine the basic properties of paracellular phosphate fluxes.
The intestine absorbs of many nutrients, among them phosphate. The absorption is mediated by active transcellular phosphate transporters and a yet poorly characterized paracellular pathway. Glucocorticoids (cortisol) and thyroid hormone control intestinal phosphate absorption but it has remained unknown whether this is mediated by active or paracellular (or both) pathways. Using mice lacking the active phosphate transporter we can dissect these pathways and examine the impact on bone health and general metabolism.
Phosphate balance is critically regulated by renal phosphate excretion and/or reabsorption mediated by a set of phosphate transporters. In patients with chronic kidney disease (CKD) renal phosphate clearance is reduced leading to excessive cardiovascular mortality. Here we will use human kidney biopsies and urinary extracellular vesicles to examine how renal phosphate transporters are regulated during the various stages of chronic kidney disease.
