Biomolecular Engineering

Manipulation of the physical and chemical characteristics of biomolecules for improved performance

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in vitro Interactions of RNAs with Recombinant Human Dicer

Mammalian Dicer is known to participate in RNA interference (RNAi) by cleaving double-stranded RNA (dsRNA) and pre-micro RNA (pre-miRNA) substrates into ~22 nucleotide short interfering RNAs (siRNAs) and miRNAs, respectively. However, recent evidence has shown that Dicer, TRBP (the human immunodeficiency virus transactivating response RNA-binding protein), and Argonaute 2 (Ago 2) form a ternary complex and that this complex is necessary for the formation of active RISC programmed with a single-stranded guide RNA. While Dicer alone has been shown to form stable complexes with dsRNAs and siRNAs, its interactions with ssRNAs have not been characterized. In this context, we are investigating if recombinant human Dicer (rhDcr) alone can bind in a sequence-independent manner to 21-nt single-stranded RNAs (ssRNAs) and investigating the possible biological roles/consequences of such behavior.

Investigators (PI is linked): S. Patrick Walton
http://www.egr.msu.edu/abel/research.html  Categories: Biotechnology, Biomedical Engineering, Biomolecular Engineering

Molecular Barcode-Labeled Aptamers for Parallel Protein Measurements

Proteomics is the measurement of all proteins in a sample. Current technologies for proteomics are usually laborious, and important information can be lost due to incomplete protein separation. We are combining two existing technologies, molecular barcodes (MBs) and aptamers, to develop a new technology for parallel protein measurements using oligonucleotide microarrays. MBs are a set of unique DNA labels that can be used to detect a single nucleic acid species from a mixed population. Aptamers are high affinity nucleic acid molecules that can bind to specific target proteins. The goal of our current research is to generate MB-containing aptamers and use them to measure the concentrations of several proteins simultaneously.

Investigators (PI is linked): S. Patrick Walton
http://www.egr.msu.edu/abel/research.html  Categories: Biomolecular Engineering, Biomedical Engineering, Biotechnology

Quantitative, Genomics-Based Measurement of Transcription Factor Levels

Inappropriate/unregulated expression of transcription factors (TFs) has been implicated in many diseases, including cancer, AIDS, and diabetes. Current methods for measurement of TF expression are inadequate for simultaneous measurement of all relevant proteins. Our work seeks to provide a genomics-based, parallel method for the measurement of TF expression using MBs and microarrays. This method will also be useful for analysis of TF binding affinities for their consensus and mutated target sequences.

Investigators (PI is linked): S. Patrick Walton
http://www.egr.msu.edu/abel/research.html  Categories: Biomolecular Engineering, Biomedical Engineering, Biotechnology

Delivery of siRNAs by Polymeric Nanoparticles

The instability of biological molecules, in particular RNAs, often limits their utility as therapeutics. However, incorporation of these molecules into delivery vectors can enhance their chemical, biological, and pharmacokinetic stability. We are investigating the use of novel polymeric nanoparticles for the delivery of siRNAs to cells in culture and in vivo.

Investigators (PI is linked): S. Patrick Walton
http://www.egr.msu.edu/abel/research.html  Categories: Biotechnology, Biomedical Engineering, Biomolecular Engineering