Research in biosensing has found importance in medical diagnostics, biomolecular analysis, and studies involving molecular pathways. DNA nanostructure-based sensors provide biocompatibility and highly specific detection based on the molecular recognition properties of DNA. My research involved developing a "DNA nanoswitch" that can detect specific nucleic acid sequences and biomarkers. Target binding induces a conformational change from the linear ‘off’ state of the nanoswitch to a looped ‘on’ state. The two states are topologically different and can be easily identified on a gel. This approach provides a single mixing step and an electrophoresis readout that is already familiar and accessible to biologists. My publications on DNA nanoswitch are here:
AR Chandrasekaran,* O Levchenko, D Patel, M MacIsaac & K Halvorsen, Addressable configurations of DNA nanostructures for rewritable memory. Nucleic Acids Res. 45: 11459-11465 (2017). [PDF] Selected as journal cover.
K Halvorsen, M Kizer, X Wang, AR Chandrasekaran & M Basanta-Sanchez, Shear dependent LC purification of an engineered DNA nanoswitch and implications for DNA origami. Anal. Chem. 89: 5673-5677 (2017). [PDF]
SELF-assembled 3D dna crystals
Designing a molecular scaffold has been the goal of DNA nanotechnology. A tensegrity triangle motif has been used to create rationally designed 3D DNA crystals. The tensegrity triangle motif contains three double helical edges connected at the vertices by four arm junctions. The triangles connect to each other via programmed sticky ends; the assembly continues infinitely in three directions leading to the formation of a crystal. Crystals with varying cavity sizes can be constructed so they can host molecules of different sizes. Some of my work involved the design and characterization of such crystals and to host a triplex-forming oligonucleotide in the 3D lattice. Here are some of my publications on this topic:
DA Rusling,^ AR Chandrasekaran,^ YP Ohayon, T Brown, KR Fox, R Sha, C Mao & NC Seeman, Functionalizing designer DNA crystals with a triple-helical veneer. Angew. Chem. Int. Ed. 53: 3979-3982 (2014). [PDF]
HO Abdallah, YP Ohayon, AR Chandrasekaran, R Sha, KR Fox, T Brown, DA Rusling, C Mao & NC Seeman, Stabilisation of self-assembled DNA crystals by triplex-directed photo-cross-linking. Chem. Comm. 52: 8014-8017 (2016). [PDF]
C Hernandez, JJ Birktoft, YP Ohayon, AR Chandrasekaran, H Abdallah, R Sha, V Stojanoff, C Mao & NC Seeman, Self-assembly of 3D DNA crystals containing a torsionally stressed component. Cell Chem. Biol. DOI: 10.1016/j.chembiol.2017.08.018. [PDF]
R Sha, JJ Birktoft, N Nguyen, AR Chandrasekaran, J Zheng, X Zhao, C Mao & NC Seeman, Self-assembled DNA crystals: The impact on resolution of 5'-phosphates and the DNA source. Nano Lett. 13: 793-797 (2013). [PDF]
Some of my research involved designing and building DNA motifs and functionalizing them using different conjugation strategies. For example, DNA tiles (such as the one shown on the left) can be tailor-made to connect with other such motifs to form arrays. The component strands can be modified and attached to functional groups via strategies such as click chemistry.
V Valsangkar,^ AR Chandrasekaran,^ R Wang, P Haruehanroengra, O Levchenko, K Halvorsen & J Sheng, Click-based functionalization of a 2'-O-propargyl-modified branched DNA nanostructure. J. Mater. Chem. B 5: 2074-2077 (2017). [PDF]
YP Ohayon, R Sha, O Flint, W Liu, B Chakraborty, HKK Subramanian, J Zheng, AR Chandrasekaran, H Abdallah, X Wang, X Zhang & NC Seeman, Covalent linkage of one-dimensional DNA arrays bonded by paranemic cohesion. ACS Nano 9: 10304-10312 (2015). [PDF]