Biology

Dhiraj Bhatia
Institute Curie

Structural DNA nanotechnology explores various nanoscale structural and functional properties of DNA to manipulate matter at nanoscale for diverse applications (1). Three dimensional architectures based on DNA polyhedra have raised particular interest in biomedical applications (2). DNA polyhedra possess an internal void bounded by a well-defined three-dimensionally structured surface (3,4). I will present the first successful delivery of quantum dots (QDs) as the internal payload of DNA icosahedra that are monofunctionalized with specific, endocytic ligands like folic acid, Galectin-3 (Gal35), Shiga toxin B-subunit (STxB6) and transferrin. Single particle tracking of Gal3/STxB-bearing, QD-loaded icosahedra reveal new observations of compartment dynamics along the endocytic pathways (7). QD-loaded DNA polyhedra bearing ligands of unique stoichiometry represent a new class of high-precision molecular imaging tools for quantitative approaches to complex biological phenomena arising from receptor clustering. Similarly, DNA caged magnetic particles were produced to purify galectin-3 enriched endocytic vesicles. Quantitative mass-spectrometry revealed new and pathway specific cargo molecules and trafficking machinery on the pre-early endosomal structures arising from Gal3 induced carriers. Using inhibitors and siRNA based screens I have validated the key cargo and cytosolic candidates involved in CLIC biogenesis and its endocytic trafficking. Our multidisciplinary and innovative approach using DNA nanotechnology and lattice light sheet microscopy has contributed immensely to fundamental understanding of formation of distinct endocytic pits via clathrin-independent carriers and the molecular anatomy of these carriers. Further, our results highlight the emerging potential of DNA devices in cell biology and biomedical applications that could enable probing and programming various biological systems as well as developing next generation tools probe and program the living systems for advanced bioengineering and biomedical applications.