~6 years ago, we set out to systematically quantify the interactions of essential metals with cellular biochemistry. I had little idea what a mammoth PhD project I'd signed up to. For years, it felt like there was no end in sight -- but here it finally is https://lnkd.in/eYzKzP3f ! ✨
We quantified growth, metallomic & proteomic responses to variations in metal availability of each essential metal routinely supplied to S. cerevisiae cells - and found that almost half the proteome responds to concentration changes of at least one metal -- we were so surprised by the results that we integrated 3 other genome scale datasets to add complementary evidence for metal-gene/protein interactions.
My favourite bit : after months of struggling to explain patterns of differentially abundant enzymes based on conventional pathway classifications, I found that if I convert the Yeast 8 GEM into a directed, bi-partite graph, annotate nodes for metal binding properties and then calculate the shortest path between each enzyme and the nearest metal-annotated enzyme - voila ! makes perfect sense ! ✨ metal requiring enzymes, often very centrally located in the metabolic network are the most likely to respond, and this effect is propagated to enzymes 1 - 2 reaction nodes away, which, due the high connectivity of metabolism, renders almost all of it metal-responsive ✨
Thank you :
✨ Oliver Lemke, Lukasz Szyrwiel, Stephan Kamrad, Johannes Hartl and Yu Chen for all the experiments and analyses we did and re-did together !
✨ my supervisor, Markus Ralser, for the unconditional support and everlasting optimism that made my PhD quite an enjoyable experience despite the painfully long and frustrating experiments !
✨ James MacRae, Jürg Bähler, Luiz Pedro Carvalho and Filipe Cabreiro for stimulating and encouraging discussions that made me look forward to thesis committee meetings 💡
✨ amazing lab-mates Clara Correia-Melo, Christoph Messner, Benjamin Heineike, Lucía Herrera-Domínguez, Michael Muelleder, Enrica Calvani, Vadim Demichev for teaching me everything I know about high-throughput experimentation & mass spectrometry and the best lab atmosphere I could've wished for as a PhD student 🙏
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