The genetic programs that drive neural development establishes the anatomic substrate that endows the mammal with the capacity to respond to external environmentally available cues. The retention of adaptive plasticity in some adult brain regions, notably the hippocampus, underlies are our ability to learn and remember. It is presumed that such adaptive plasticity must be mediated by selective changes in gene and protein expression within neurons that comprise the anatomic substrate. To understand the temporal and ordered sequence of molecular events that result in adaptive plasticity we need novel tools that must be designed to work in concert. This application will develop and validate such methodology in a well-described neural system. This application will result in the creation of the following four interleaved and novel technologies that will be scalable and broadly applicable. These new technologies are: l) A method and reagents for producing single gene changes within an experimentally determined number of neural cells in the intact nervous system. 2) A combined single cell microdissection and mRNA amplification approach to profile all mRNAs from genetically altered cells or others of interest. 3) A bioorganic transistor to detect change in the levels of different proteins from genetically altered cells or others of interest. 4) Bioinformatics methods to extract genetic regulatory networks from mined profile data.
| Li, Huixiang; Rothberg, Lewis (2005) Detection of specific sequences in RNA using differential adsorption of single-stranded oligonucleotides on gold nanoparticles. Anal Chem 77:6229-33 |
| Li, Huixiang; Rothberg, Lewis J (2004) Label-free colorimetric detection of specific sequences in genomic DNA amplified by the polymerase chain reaction. J Am Chem Soc 126:10958-61 |
| Li, Huixiang; Rothberg, Lewis J (2004) DNA sequence detection using selective fluorescence quenching of tagged oligonucleotide probes by gold nanoparticles. Anal Chem 76:5414-7 |
| Li, Huixiang; Rothberg, Lewis (2004) Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles. Proc Natl Acad Sci U S A 101:14036-9 |
| Bijlani, Rahul; Cheng, Yinhe; Pearce, David A et al. (2003) Prediction of biologically significant components from microarray data: Independently Consistent Expression Discriminator (ICED). Bioinformatics 19:62-70 |
