Nikos S Hatzakis, Department of Chemistry, Faculty of Science, University of Copenhagen

Novonordisk center for Protein Research, Faculty of Health, University of Copenhagen
Department of Pediatrics Boston Children hospital Harvard Medical school

Unleashing the power of single-nanocontainer readouts and deep learning: Pushing the Biomolecular recognition detection to new frontiers

Biomolecular recognition is underlying and controlling all biological and chemical processes. However Screening of biomolecular recognition often suffers from challenges such as long running time , high man power as well as excessive materials cost. To surpass these challenges we are developing and implementing miniaturized assays for ultra-sensitive and high-throughput screening of biomolecular interactions. To rapidly and reliably analyze and classify the multidimensional multi terabyte data we are developing automated technologies based on deep learning

Here I will present our recent work on the development and implementation miniaturized screening assay for ultra-sensitive and high-throughput readout at the single-particle level^1-3 to explore a)  DNA-DNA recognition and sub-attolitter cargo delivery, b) transporter function and c) how membrane properties affect protein function. A key aspect of this work is the single-particle combinatorial multiplexed liposome fusion mediated by DNA for parallelized multistep and non-deterministic fusion of individual subattolitre nanocontainers (SPARCLD). Using high-density arrays of surface-tethered target nanocontainers (~42,000 containers per mm²) allowed real time recordings of >16,000 fusions and 566 distinct fusion sequences within hours. Our toolboxes offers screens of entire combinatorial multiplex using only picograms of material and is implanted for screening transporter function and label free DNA biosensing.

Relevant publication of my group

1. Malle, M. G. et al. Single-particle combinatorial multiplexed liposome fusion mediated by DNA. Nat. Chem. 2022, 14, 558.
2. Jensen, S. B. et al. Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase. Nat. Commun. 2021, 12, 2260.
3. Thomsen, R. P. et al. A large size-selective DNA nanopore with sensing applications. Nat. Commun. 2019, 10, 5655.
4. Schmidt, S. G. et al. The dopamine transporter antiports potassium to increase the uptake of dopamine. Nat. Commun. 2022, 13, 2446.