Subsystems Development and Genome Annotation
Within 2–3 years we will all have access to over a thousand sequenced genomes. This data will grow to become the central resource in modern biology. Annotating this collection is the core challenge of modern bioinformatics. A new approach to annotation based on idea of subsystems promises to dramatically improve the quality and utility of annotations. A subsystem is a set of functional roles that together implement a specific biological process (e.g. pathway) or structural complex. The SEED annotation environment uses the genomic information to create, curate, and exchange of subsystems. The approach and technology provide one way to involve many domain experts in the genome annotation process. The technology for developing these subsystems now exists, the technologies for supporting automated addition of new genomes to the collection of populated subsystems is now being developed, and the initial collection is being made available to the research community.
NAD biosythesis
The NAD biosynthetic pathway has been analyzed by an arsenal of comparative genomics tools. The NAD-specific regulon operated by a novel transcription factor was described in Gram-positive bacteria, where it regulated both NAD biosynthetic enzymes and new NAD-related transporters. Experimental verification of the predicted nicotinate-specific repressor will be conducted.
NAG metabolism
We analyzed the metabolic pathway of N-acetylglucosamine (NAG) catabolism using a combination of comparative genomics and experimental techniques. It is resulted in identification of novel enzymes and transporters implicated in NAG metabolism and previously missed in many bacterial species. We described two novel transcriptional networks for NAG utilization genes in various proteobacteria. Experimental functional verification of the predicted NAG genes in Shewanella oneidensis and Thermotoga maritima is underway.
Proteolytic events: posttranslational modification
Our primary goal in proteolytic events research is to elucidate the pathways of protein cleaved cascades and their regulations in vivo. In proteolytic events, protease binds to and cleaves its substrate. These events are indispensable to mature immature proteins, activate inactive proteins and degrade unnecessary proteins. And, these events are also involved in diseases such as Alzheimer's disease, cancer, viral infection, emphysema and among others. Currently, we are developing the CutDB (http://cutdb.burnham.org) annotation database which organize the information of proteolytic events.