Millis Hall G22B
Lab: Millis Hall G25 & G11
Degree: PhD, Iowa State University
Biochemistry, medicinal, structural DNA nanotechnology, spectroscopy, nanotechnology, inorganic nanomaterials, nucleic acids, gene delivery
- Postdoc at the US Naval Research Lab & George Mason University, Washington DC
- PhD in Bioinformatics & Computational Biology, Iowa State University (2016)
- BEng in Biotechnology, Delhi College of Engineering (2010)
High-throughput precision over materials in the 1-100 nanometer regime is an enormous challenge to be overcome solely with the help of top-down synthesis strategies. In recent years, synthetic DNA has proven to be an excellent biomaterial that can be programmed to chemically couple with other organic and inorganic molecules and achieve such nanoscale control and consequently enhance their photophysical, chemical, and therapeutic properties. Therefore, the overarching goal of the Mathur Nano Lab is to leverage the architectural and biophysical attributes of oligonucleotides as effective means to facilitate and augment the abilities of materials in the nanoscale. We address fundamental biochemical challenges in the delivery of nucleic acid payloads to mammalian cells. Through these research programs, students will be trained in nanotechnology, nucleic acid chemistries, and biochemical analytical tools to become the next generation of STEM researchers.
The group has four active interests:
- Optoelectronic tailoring – working with the Crespo and Parker groups in the department, we are interested in achieving higher control over the position and orientation of optically-active dye molecules by building DNA based scaffolds and templates. The Parker group assists in informing the design and interpreting the results with computational analysis of the dye-DNA constructs while the Crespo group spearheads the experimental probing of the spectral properties of these constructs.
- Gene origami – we are interested in biochemical mechanisms of merging the architectural abilities of DNA nanotechnology with the putative biological role of DNA as a gene storage and transport molecule. We are developing molecular platforms to probe the transcription and transfection efficacy of DNA nanoparticles that encode protein-expressing sequences.
- Cytosolic stability of DNA nanoparticles – DNA nanotechnology has also proven to be a viable biomaterial for developing diagnostic and therapeutic platforms. However, it is evident that a knowledge gap persists in understanding the stability of DNA-based nanostructures in the mammalian cytosol. To that end, we have found that the DNA structure design itself can be tailored to tune their half-life within the cytosol, which potentially provides a strategy to develop DNA-based carriers with better drug-release capabilities. Herein, we use an approach to identify the cytosolic stability of small DNA nanostructures that combines single-cell microinjection with multi-step Förster resonance energy transfer (FRET) and confocal microscopy in order to measure the extent of DNA structural degradation directly in mammalian cells.
- Molecular cognition – As Synthetic DNA nanotechnology is being widely utilized in a diverse range of applications (such as biomedicine, light-harvesting, nanoscale templating, catalytic cascades, photonics, plasmonics, and many more!) focus on workforce development requires a careful look and evaluation. This means – how is the next generation of students and trainees learning about synthetic DNA nanotechnology? Are there any curricula/books/courses that are tailored to the interdisciplinary nature of the field? Does education in different STEM disciplines that are important for DNA nanotechnology facilitate active learning and collaboration? And more importantly, given the three-dimensional nature of DNA nanostructures, can we leverage modern immersive tools to facilitate learning and collaboration? In this work, overarching questions such as these are explored. We collaborate closely with Drs. James Lathrop and Stephen Gilbert at Iowa State University to identify STEM training and learning in the field and the role 3D/virtual reality tools can play in enhancing cognition. We have developed a platform called MolCog (from Molecular Cognition) which is a VR-enabled tool to build, manipulate, and learn about DNA origami structures. Ongoing work focuses on how to develop modules that make it fun to learn about DNA origami.
- Mathur, D., K.E. Rogers, S.A. Díaz, M.E. Muroski, W.P. Klein, O.K. Nag, K. Lee, L.D. Field, J.B. Delehanty, and I.L. Medintz. 2022. Determining the Cytosolic Stability of Small DNA Nanostructures In Cellula. Nano Lett, DOI: 10.1021/acs.nanolett.2c00917.
- Mathur, D., and I.L. Medintz. 2019. The Growing Development of DNA Nanostructures for Potential Healthcare-Related Applications. Adv Healthc Mater 8:e1801546, PMID:30843670.
- Mathur, D., A. Samanta, M.G. Ancona, S.A. Díaz, Y.C. Kim, J.S. Melinger, E.R. Goldman, J.P. Sadowski, L.L. Ong, P. Yin, and I.L. Medintz. 2021. Understanding Forster Resonance Energy Transfer in the Sheet Regime with DNA Brick-Based Dye Networks. ACS Nano 15(10), 16452-16468, PMID: 34609842.
- Mathur, D., and E.R. Henderson. 2013. Complex DNA nanostructures from oligonucleotide ensembles. ACS Synth Biol 2:180-185, PMID:23656476.