Research Bio
Research in the Miller group focuses on two fundamental areas: the control of biomolecular interactions through the synthesis of new small-molecule probes, and the observation of biomolecular interactions through the development of novel optical sensing technologies. In the area of control, we are particularly interested in the sequence-selective recognition of RNA. New RNA sequences with important functions in basic biology and human health and disease are being discovered at an ever-increasing rate, and yet our ability to target these sequences specifically is still at a rudimentary stage. To address this gap, we are applying techniques of molecular design and a novel combinatorial method of small-molecule evolution called Dynamic Combinatorial Chemistry, which allows us to rapidly "prototype"
sequence-selective RNA binding molecules. Thus far we have used this methodology to RNA targets important in Myotonic Dystrophy and HIV. Protein-targeted small-molecule discovery projects are also of interest, and current projects include the mechanism of tight junction formation and the transport of beta-amyloid across the blood-brain barrier. To the end of achieving better methods of observing biomolecular interactions, our group has a longstanding program in the use of the optical properties of nanostructured materials as the basis for new biosensors and diagnostic tools. Two examples of current efforts include Arrayed Imaging Reflectometry (AIR) and sensors based on two-dimensional photonic crystals (2-D PhC). AIR relies on the creation of a near-perfect antireflection coating on the surface of a silicon chip; binding of a biomolecular target destroys this antireflective condition and is visible by a change in reflected light. This allows for highly multiplexed (10's to 1000's of targets) and quantitative detection. Photonic crystal sensors, on the other hand, offer the possibility of ultrasensitive detection: for example, a major long-term goal of our work is the production of sensors that can effectively detect one virus in a blood sample.
2014 Feb 13
Ofori LO, Hilimire TA, Bennett RP, Brown NW, Smith HC, Miller BL. "High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity." Journal of medicinal chemistry.. 2014 Feb 13; 57(3):723-32. Epub 2014 Jan 15. |
2014 Feb 1
Yadav AR, Sriram R, Carter JA, Miller BL. "Comparative study of solution-phase and vapor-phase deposition of aminosilanes on silicon dioxide surfaces." Materials science & engineering. C, Materials for biological applications.. 2014 Feb 1; 35:283-90. Epub 2013 Nov 20. |
2014 Jan 21
Lifson MA, Basu Roy D, Miller BL. "Enhancing the detection limit of nanoscale biosensors via topographically selective functionalization." Analytical chemistry.. 2014 Jan 21; 86(2):1016-22. Epub 2013 Dec 27. |
2014 Jan 21
Yadav AR, Mace CR, Miller BL. "Examining the Interactions of the Splicing Factor MBNL1 with Target RNA Sequences via a Label-Free, Multiplex Method." Analytical chemistry.. 2014 Jan 21; 86(2):1067-75. Epub 2014 Jan 09. |
2013 Jun 15
Pal S, Yadav AR, Lifson MA, Baker JE, Fauchet PM, Miller BL. "Selective virus detection in complex sample matrices with photonic crystal optical cavities." Biosensors & bioelectronics.. 2013 Jun 15; 44:229-34. Epub 2013 Jan 15. |
