Molecular Recognition in Biological Systems and Bioinformatics

Protein structure and function; RNA base-modification enzymes; rare amino acids (e.g. selenocysteine); comparative genomics to identify novel biochemistry; oligomeric assembly; metabolic pathways.

Structure biology of the RNA modification processes

Our goal is to understand the enzymatic processing of the anticodon domains of the tRNAs. tRNAs are most heavily modified amongst all the RNAs that contains about 100 known natural base modifications. Extensive modifications of the 34th (wobble base) and the 37th (3' to the anticodon) positions in several tRNAs play a crucial role in accurate codon recognition and reading-frame maintenance. In addition, several modified anticodons contribute to genetic code plasticity. Wobble modification defects in mitochondrial tRNAs are implicated in several disease states. Given the central role of the decoding event in the cellular physiology, very little is understood about the enzymatic targeting and processing of the tRNA anticodons. Therefore, we are studying the mechanism of these processes using crystallographic and other biophysical techniques. Of special interest to us are those eukaryotic enzymes that display multi-site specificity and perform intron-dependent tRNA modifications. Furthermore, we shall explore proteomic (mass-spectrometric) approaches to identify the complete set of anticodon processing enzymes in yeast.

Nano-scale artificial protein assembly design using a novel bio-mimetic approach

Our goal is to explore a novel, bio-mimetic method to design and build nano-scale assemblies using functional protein modules as building blocks. Nano-biomaterial design is an emerging frontier of science that utilizes bio-molecules to manufacture devices with novel properties. However, precise positioning of molecules at nano-scale poses a challenge, which could be bypassed by imitating natural self-assembly processes. In order to understand the rules of the self-assembly in biological pathways, we are developing a bio-mimetic method to position a set of target protein modules in an ordered manner to form synthetic, supra-molecular assemblies. This project ties in with several frontiers of chemistry and biology, while taking advantage of the post-genomic information explosion in the area of protein sequence, structure and biological pathway databases. Success of our novel design approach will likely lead us to build artificial reaction-factories for industry and metabolic engineering purposes, biodegradable nano-vehicles for multiple drug delivery or in vivo drug synthesis in cancer therapeutics, protein arrays and other novel biomaterials.

• Crystallographic, structure and sequence analysis softwares
• Computer programming (mainly PERL)
• Designed server: http://www.doe-mbi.ucla.edu/~neel/RSA.php

Pseudouridine synthase (TruB, pus1p)

Dyskeratosis congenital - a disorder of defective telomere maintenance; Mitochondrial myopathy and sideroblastic anemia (MLASA); selenium micronutrient

• X-ray crystallography
• biological structure and sequence analysis
• Genomic data analysis

http://genomebiology.com/2005/6/9/R79/?mkt=87266

http://www.ncbi.nlm.nih.gov/pubmed/12842039?dopt=Books