Associate ProfessorPh.D., University of South Florida
PDF, California Institute of Technology
Email Dr. Jonathan Rast
Gene Regulatory Programmes that ControlAnimal Immunity
Research in our laboratory is concerned with characterizing the gene expression programs that underlie animal immunity. These gene regulatory networks encompass transcription regulatory proteins, the DNA control sequences to which they bind and the signaling systems which convey nuclear states among cells. We are interested in understanding regulatory networks that direct immunocyte specification and thereby set up programs for innate immune function. We employ the embryo and larva of the purple sea urchin ( Strongylocentrotus purpuratus ) as an uncomplicated experimental system. These animals offer advantages for this work including the availability of enormous quantities of staged embryos, highly efficient transgenesis and the ability to specifically perturb gene function using antisense and transgenic technologies. Importantly, sea urchins are echinoderms, a sistergroup of the chordates, and thus they share a genetic heritage with the vertebrates that is critical for our comparative investigations. The purple sea urchin genome sequence reveals an innate immune system of unprecedented diversity that is rich with experimental opportunities to better understand our own immune system. We approach these issues from three directions:
1.) We are characterizing expression of sea urchin homologs of transcription factors that are well known as regulators of hematopoiesis and immunity in vertebrates. Genes currently being characterized include homologs of vertebrate GATA-1/2/3, PU.1/Spi-B/Spi-C, E2A/HEB/ITF-2, SCL/Tal-2/Lyl-, and Id- 1/2/3/4. All of these genes are important in the development of larval immune cells.
2.) In a second approach, we are characterizing genes that are responsible for immune recognition, regulation and effector functions. Genes in this category include those encoding immense superfamilies of recognition proteins such as toll-like receptors (TLRs), Nod/Nalp-like proteins and SRCR domain proteins, genes that encode immune signaling molecules such as TNF family members and IL17 homologs, gene families with characteristics of antimicrobial peptides, and perforins. We are also looking at a variety of genes with homologs in the vertebrate adaptive immune system.
3.) Finally we are bringing together developmental and recognition functions in gene regulatory models that describe immune mechanisms that carry out gut immunity in the simple larval model.
Work in this simple model reveals conserved gene regulatory circuitry that can then be characterized in more complicated vertebrate systems. The sea urchin also provides an invaluable set of “natural experiments” that illuminate the workings of our own immune system and present us with entirely novel solutions to the immune challenges all animals face.
Link to Sunnybrook website: http://sunnybrook.ca/team/member.asp?t=12&m=139&page=172
List of Key Publications:Link to Pubmed Publications
Rast JP, Smith LC, Loza-Coll M, Hibino T, Litman GW. 2006. Genomic insights into the immune system of the sea urchin. Science 314:952-6.
Sea Urchin Genome Sequencing Consortium. 2006. The genome of the sea urchin Strongylocentrotus purpuratus. Science. 314: 941-52.
Hibino T, Loza-Coll M, Messier C, Majeske AJ, Cohen AH, Terwilliger DP, Buckley KM, Brockton V, Nair SV, Berney K, Fugmann SD, Anderson MK, Pancer Z, Cameron RA, Smith LC, Rast JP. 2006. The immune gene repertoire encoded in the purple sea urchin genome. Dev Biol. 300:349-65.
Fugmann SD, Messier C, Novack LA, Cameron RA, Rast JP. 2006. An ancient evolutionary origin of the Rag1/2 gene locus. Proc Natl Acad Sci U S A. 103:3728-33.
- Nicholas Schuh