Title

Speaker: Jemima Burden
Institution: Institution
Place: Jerónimo Forteza conference room, CIPF

Abstract:

Abstract.

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The role of protein kinases and phosphatases in the regulation of autophagy

Speaker: Prof. Joern Dengjel
Institution: University of Fribourg, Fribourg, Switzerland
Place: Jerónimo Forteza conference room, CIPF

Abstract:

Autophagy is an evolutionary conserved, vital cellular recycling pathway that is often found dysregulated in human diseases. Depending on the subtype, single proteins or entire organelles can get degraded in lysosomes, either selectively or in a less selective, bulk manner. We study the regulation of macroautophagy in which double membrane organelles, i.e. autophagosomes, are formed de novo to enwrap cytoplasm and target it for lysosomal degradation. Protein and lipid kinases and phosphatases regulate autophagy initiation as well as autophagosome maturation and fusion with lysosomes. Using protein biochemistry and mass spectrometry-based proteomics we develop in vitro and in vivo assays to study kinase-phosphatase crosstalk focusing on the serine-threonine kinase complex ULK1 and PP1 and PP2A phosphatase complexes. We could show that the regulatory PP2A subunit Striatin is a bona fide ULK1 target serving as positive feedback to promote autophagy-dependent protein turnover. Currently, we study a deep interactome of the ULK1 holo-complex to identify new protein-protein interactions that are critical for autophagy regulation.

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Title

Speaker: Franca Rosa Guerini
Institution: Institution
Place: Jerónimo Forteza conference room, CIPF

Abstract:

Abstract.

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Title

Speaker: Evan Hernando-Monge
Institution: Institution
Place: Jerónimo Forteza conference room, CIPF

Abstract:

Abstract.

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Repurposing drug delivery systems for diagnostics

Speaker: Prof. Joern Dengjel
Institution: Faculté de Pharmacie, Université de Montréal, Montréal, Canada
Place: Jerónimo Forteza conference room, CIPF

Abstract:

In the last two decades, a number of drug delivery systems were repurposed for diagnostic applications. Traditional uses of diagnostic delivery systems are nanocarriers of diagnostic cargo (e.g., contrast agents) with controlled release kinetics or active targeting properties. In this seminar, I will demonstrate how established delivery systems can be used for diagnostics in less conventional ways. First, I will present the development of an enzyme-loaded vesicular reaction compartment for the quantification of lactate in whole blood. Isolating the lactate-sensing reaction in the liposomal lumen allowed this reaction to occur in whole blood as interfering substances were incapable of crossing the membrane. This vesicular reaction compartment forms the basis of a novel blood lactate assay for bedside use in sepsis. The fluorescence assay was tested in fresh human blood in an Institutional Review Board-approved study and successfully combined with a portable fluorometer. This system highlighted how the selectively permeable membrane of liposomes could be utilized to isolate an enzymatic reaction in order to enable it in a prohibiting matrix. Second, I will present the development of a series of novel non-releasing hydrogels for diagnostic applications. Hydrogels are widely used in tissue engineering and drug delivery, and their localization is tied to their function. As means for hydrogel localization in the body are limited, we developed a new and broadly applicable method to track hydrogels by encapsulating a clinically used oil-based contrast agent. This non-releasing system was visualized in mice using computed tomography. Another example of a non-releasing hydrogel is a pH-sensing diagnostic wound dressing for chronic wounds. Hydrogels loaded with pH-sensitive fluorescent microparticles were developed and sensed the pH in a clinically relevant range on dorsal mouse wounds. The dye was highly retained on microparticles in the presence of biological fluids to minimize the risk of wound exposure to the dye. These liposomal and hydrogel systems highlight the high versatility and usefulness of drug delivery systems for diagnostic applications.

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