| Summary: | <p>Alzheimer’s disease (AD) and cardiovascular diseases (CVDs) pose a major challenge in the coming decades considering an increasingly ageing population and demographic changes. MYLIP, also known as inducible degrader of the LDL receptor (IDOL) is an E3 ligase that is involved in the downregulation of lipoprotein receptors: the low-density lipoprotein receptor (LDLR) and the very low-density lipoprotein receptor (VLDLR). LDLR and VLDLR are involved in plasma cholesterol clearance in the liver and Aβ plaque removal in the brain, respectively. Therefore, MYLIP is of great interest as a potential therapeutic target for two of the biggest challenges in aged care. Here, I have developed methods to express MYLIP and other proteins in the ubiquitination cascade of the lipoprotein receptors, assays to screen small molecule libraries for inhibitors of the function of MYLIP and used the assay to conduct a pilot screen with a subset of a diversity library held by the Oxford Drug Discovery Institute. The resulting data set was then analysed in a workflow in the software that I have developed in this project.</p>
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<p>Reliable, easy to use data analysis software is a corner stone of drug discovery efforts. Especially in academia, there exists a need for easy to use, affordable, reliable, and adaptable software that can be used in place of disparate templates for different pieces of software that have often been developed by long gone group members. Here, I have developed such a software that offers ease of use, is modular and allows for quick development of new workflows for novel assays. In addition, it is easily integrated into an Oracle database. Biophysical and Biochemical Quantifier and Qualifier (BBQ) is now used in our department for the analysis of routine peptide displacement assays, enzymatic assays, and differential scanning fluorimetry, to determine IC50 values, Δ<em>T</em><sub>m</sub> values, and screening compound libraries in single dose screens.</p>
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