Briggs website - Home Page

University of California, San Diego

Division of Biological Sciences

Section of Cell & Developmental Biology

Research Highlights

Embryonic stem cell self-renewal
We are mapping the regulatory networks that enable human and mouse embryonic stem (ES) cell self-renewal. Whole cell proteome profiles using LC ESI MSMS are revealing new genes whose products are unique to ES cells. Whole phosphopeptide profiles have shown us that many of these regulators of self-renewal are phosphorylated. We are working to determine the significance of this phosphorylation and to identify the protein kinases that are responsible. Our aim is to bridge the gap between studies of transcriptional regulation and cell signaling in ES cells.

Plant infectious disease
We are studying the protein determinants of disease and disease resistance in plants to infection by the nematode, Meloidogyne incognita. Whole tissue proteome profiles using LC ESI MSMS are revealing new genes whose products are induced or repressed by infection. Whole phosphopeptide profiles have shown us that many induced regulatory proteins are phosphorylated. We are working to determine the significance of this phosphorylation by mutant analysis and by identifying proteins that co-immunoprecipitate. Our goals are to understand the recognition and signaling systems that lead to susceptibility in one instance and resistance in the other, and to create new mechanisms for recognition and disease resistance.

Recent Publications
	"Discovery and revision of Arabidopsis genes by proteogenomics." Proceedings of the National Academy of Sciences of the United States of America 105(52): 21034-8, Castellana, N. E., S. H. Payne, Z. Shen, M. Stanke, V. Bafna and S. P. Briggs (2008). We isolated proteins from a sample of Arabidopsis tissues and determined the amino acid sequences of 144,079 distinct peptides by tandem mass spectrometry. The majority of the peptides (126,055) resided in existing gene models (12,769 confirmed proteins), comprising 40% of annotated genes. Surprisingly, 18,024 novel peptides were found that do not correspond to annotated genes. Using the gene finding program AUGUSTUS and 5,426 novel peptides that occurred in clusters, we discovered 778 new protein-coding genes and refined the annotation of an additional 695 gene models. The remaining 13,449 novel peptides provide high quality annotation (>99% correct) for thousands of additional genes. Our observation that 18,024 of 144,079 peptides did not match current gene models suggests that 13% of the Arabidopsis proteome was incomplete due to approximately equal numbers of missing and incorrect gene models. The peptides and predicted models can be accessed here. The paper can be downloaded here.
	"Direct identification of the Meloidogyne incognita secretome reveals proteins with host cell reprogramming potential." PLoS pathogens 4(10): e1000192, Bellafiore, S., Z. Shen, M.-N. Rosso, P. Abad, P. Shih and S. P. Briggs (2008). We have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions. Others have regulatory domains that could reprogram cells. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi), suggesting a common parasitic behavior and a possible conservation of function between metazoan parasites of plants and animals. The paper and identified proteins can be downloaded by clicking the links.