UK-based Iceni Diagnostics is using fluorescent probe technology to explore the structure and metabolism of glycogen, as part of a wider pan-European project using ‘systems medicine’ to investigate glycogen storage diseases (GSD).
GSDs are rare diseases based on specific enzyme deficiencies involved in the breakdown or synthesis of glycogen. Iceni Diagnostics researcher Gaia Fancellu is looking into the characterisation of the branched polymer in healthy people versus GSD patients as part of the Polymers in the Liver: Metabolism and Regulation (PoLiMeR) consortium.
PoLiMeR is taking a ‘systems medicine’-based perspective, creating a computational model of the glycogen breakdown process. When this model is fed with patient data it will have the potential to provide a personalised diagnosis and treatment strategy for each individual.
The €4m project acts as a four-year training network which provides innovative research training in personalised systems medicine, and supports 15 PhD students including Fancellu.
Fancellu said: “I am doing this following a top-down approach. The first step will be based on breaking down glycogen using specific enzymes to determine polymer length, positions and number of branching points at different cleavage points. The results will be analysed by high-performance chromatography and mass spectrometry.
“In the second step, I’ll work with fluorescent probes to detect the structure of glycogen based on changes in fluorescence, using spectrophotometer as the reference tool to study the results.”
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Fluorescent probes are chemical compounds that act like a molecular rotor, changing colour when its movement is constrained. When glycogen breaks down a cell changes in viscosity, so a fluorescent probe can indicate microenvironmental changes within a live cell.
Fancellu said: “I’ll be using this same fluorescent probe, in a different environment, to detect any changes in the internal viscosity, wavelength, pH and, ultimately, structure of the glycogen cells.”
Funding for this project has been achieved through Horizon 2020, the European Union’s current funding framework to support technological innovation and research on the continent.