George A.M. Cross, Ph.D.
André and Bella Meyer Professor Emeritus
Trypanosomes remain a problem for humans and other animals throughout large regions of Africa and South America. African sleeping sickness and American Chagas disease are invariably fatal, though it may take weeks or years to succumb, depending on the species and the strain. Cross’s past research and current interests focus on how the African trypanosomes evade our immune systems, which has prevented the development of a vaccine, and on the novel biochemical and genetic mechanisms employed by these organisms. Trypanosomes branched very early in eukaryotic evolution, and they have significant and sometimes bizarre variations from the conventional mechanisms of gene expression. Research on trypanosomes can shed light on how more complex, higher eukaryotic regulatory systems have evolved.
Trypanosoma brucei causes African sleeping sickness and is transmitted by the Glossina species, commonly known as the Tsetse. Ten million copies of a single glycoprotein form the surface coat of the parasite, a dense structure that surrounds the entire cell body and the flagellum. Using recombinatorial mechanisms, trypanosomes possess an infinite capacity for switching among the thousands of genes that encode members of the variant surface glycoprotein (VSG) family, allowing infections to evade the host immune system, so the parasites proliferate indefinitely, until death of the host.
Cross was the first to identify the VSG family and characterize VSG genes, which led to the discoveries of messenger RNA trans-splicing and a mechanism for protein anchoring to the cell membrane, called glycophosphatidylinositol (GPI) anchoring, which has since been found to be used in a wide range of organisms, including in some important human proteins. Trypanosomes use GPI anchoring to a greater extent than almost any other organism, and there are some unique features of GPI anchoring in these parasites that are still not well understood.
Born in Cheshire, England, Cross received his undergraduate degree in 1964 and his Ph.D. in microbial biochemistry in 1968 from the University of Cambridge. From 1970 to 1977 he worked in the Medical Research Council Biochemical Parasitology Unit in Cambridge. He then joined the Wellcome Research Laboratories of the Wellcome Foundation in England, where he headed the department of immunochemistry, which later became the department of molecular biology. Cross came to Rockefeller in 1982. In 1984 Cross was a recipient of the Paul Ehrlich and Ludwig Darmstaedter Prize, awarded in Germany, and he received the Chalmers Memorial Medal of the Royal Society of Tropical Medicine and Hygiene in 1983. He is a fellow of The Royal Society.