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.
2016 Sep 1
McAnany JD, Reichert JP, Miller BL. "Probing the geometric constraints of RNA binding via dynamic covalent chemistry." Bioorganic & medicinal chemistry. 2016 Sep 1; 24(17):3940-6. Epub 2016 Feb 24. |
2016 Mar 15
Carter JA, Triplett E, Striemer CC, Miller BL. "A label-free, multiplex competitive assay for small molecule pollutants." Biosensors & bioelectronics. 2016 Mar 15; 77:1-6. Epub 2015 Aug 29. |
2016 Jan 15
Hilimire TA, Bennett RP, Stewart RA, Garcia-Miranda P, Blume A, Becker J, Sherer N, Helms ED, Butcher SE, Smith HC, Miller BL. "N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA." ACS chemical biology. 2016 Jan 15; 11(1):88-94. Epub 2015 Nov 03. |
2015 Jul
Miller BL. "mRNA regulation: A patch for a splice." Nature chemical biology. 2015 Jul; 11(7):454-5. |
2015 Jun
Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, Abner EL, Petersen RC, Federoff HJ, Miller BL, Goetzl EJ. "Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study." Alzheimer's & dementia : the journal of the Alzheimer's Association. 2015 Jun; 11(6):600-7.e1. Epub 2014 Aug 15. |
