I always had a very strong interest in the relationship of structure and dynamics in protein function. This was the reason why, after finishing a Diploma in Pharmacy and a MSc/BSc in Molecular Biology at the University of Vienna, I decided to join to the group of Dr Paul Schanda, a specialist in protein dynamics by NMR, at the IBS (Grenoble, France). During my PhD I studied the dynamic interaction of the mitochondrial intermembrane space chaperone TIM910 with several membrane protein substrates. In the course of this project I set up a purification procedure and an interaction assay for the TIM910 chaperone and its highly aggregation prone substrates. I was able to characterise this highly challenging system using an integrative structural biology approach. I used NMR and yeast mutational experiments to determine the membrane protein binding site and analytical ultracentrifugation, small angle X-ray scattering and molecular dynamics to define the overall structure of the complex between the chaperone and the membrane protein partners. I have published three articles on this topic, with two of them as first author (Weinhäupl K et al, Cell. 2018, doi:10.1016/j.cell.2018.10.039; Sucec I et al Sci Adv. 2020, doi:10.1126/sciadv.abd0263; Weinhäupl K et al, Structure. 2021, doi:10.1016/j.str.2021.04.009) and I was awarded the "Prix Nine Choucroun" for the best PhD thesis in Biophysics/Biochemistry in France in 2017-2018. In a side project I also worked on the ClpC1 protein of Mycobacterium tuberculosis to understand the importance of protein dynamics in substrate recognition and drug action. I demonstrated that arginine-phosphate binding to the ClpC1 N-terminal domain induces millisecond dynamics. I showed that these dynamics are caused by conformational changes and do not result from unfolding or oligomerization of this domain. Cyclomarin binding to this domain specifically blocked these N-terminal dynamics. On the basis of these results, I proposed a mechanism of action involving cyclomarin-induced restriction of ClpC1 dynamics, which modulates the chaperone enzymatic activity leading eventually to cell death (Weinhäupl K et al, J Biol Chem. 2018, doi:10.1074/jbc.RA118.002251; Felix J et al, Sci Adv. 2019, doi:10.1126/sciadv.aaw3818). After working one year in the Hospital pharmacy of the Kaiser Franz-Josef-Spital in Vienna, I joined the lab of Dr Morais-Cabral at the i3S in Porto in July 2019 to work on the influence of the second messenger cyclic-di-AMP on potassium homeostasis. In September 2019 I was awarded a fellowship from the Austrian Science Fund to continue my research on this topic and focus more specifically on the structure and function of the diadenylate cyclase CdaA. I was also awarded a highly competitive HFSP fellowship, which I declined. Since December 2020 I hold a junior researcher position at i3S funded through the "FCT Stimulus of Scientific Employment, Individual Support 2018 Call". In 2021, as PI, I was awarded an Instruct remote Internship to study and optimise the CdaA-CdaR-GlmM complex for cryo-electron microscopy and in 2022 a "FCT exploratory project" to continue my work on this topic. To support my training as a cryo-electron microscopist I hold several international and national collaborations. Most importantly with Prof. Thomas Marlovits from CSSB Hamburg, where I learned cryo-EM techniques during several visits, but also with Dr Jan Felix from the University of Ghent and Dr Marcos Gragera and Dr Teresa Bueno from CSIC Madrid on the M. tuberculosis drug target ClpC1 as well as with Dr Oliver Schraidt from INL Braga and Dmitry Semchonok from ITQB, Lisbon. In December 2023 I have obtained an Assistant researcher position in the "Individual Call to Scientific Employment Stimulus - 6th Edition" to continue my research on new antibiotic targets using cryo-EM.