Steven E. Jacobsen, a plant biologist at UCLA whose research on a weed has led to new understanding of an important mechanism for regulating gene expression in developing organisms, has been named an investigator of the Howard Hughes Medical Institute.
Jacobsen was one of the nation's 43 most promising scientists named by the institute. The Howard Hughes Medical Institute Investigator Program seeks highly creative investigators at distinguished universities, research institutes and medical schools across the United States involved in leading-edge biological and biomedical research. The investigators remain at their home institutions, working in laboratories funded by the institute.
Jacobsen, a professor in the UCLA Department of Molecular, Cell and Developmental Biology, found that the mild-mannered weed, Arabidopsis, is a model for understanding DNA methylation, an important mechanism for regulating gene expression in developing organisms.
Jacobsen, who grew up on a farm in Merced, Calif., originally had planned on working in applied plant science, but that vision changed when he studied Arabidopsis in graduate school; he now is recognized as a leading authority on DNA methylation.
An organism's essential blueprint lies in the sequence of nucleotides that make up its genes. However, the expression of these genes can be altered in many ways without changing the sequence information. Changes in gene expression that do not modify the fundamental gene sequence are known as epigenetic gene regulation, and one of the primary ways cells do this is through DNA methylation; cells can turn off, or silence, particular genes by chemically attaching methyl groups to their surface.
This process of methylation is fundamental to controlling growth and development in both plant and animal cells, and is important in some cancers: for example, cancer cells silence tumor suppressor genes through methylation and, as a result, uncontrolled cell growth occurs.
Eukaryotic DNA methylation has been a puzzle because its function has been controversial, and also because it has been difficult to understand how DNA methylation in animals can be targeted to small regions of the genome. Jacobsen and others are gaining on this problem by studying the phenomenon of epigenetic mutations - alleles, or alternative forms, of developmentally important genes that have been silenced by DNA methylation. Methylation mutations can be used for classical genetic studies, because plants inherit them in the same patterns that they inherit genes.
Jacobsen is recognized for studies of the "Clark Kent" mutations in Arabidopsis, which affect the flower development gene "Superman." Normally, the "Superman" gene makes sure that a flower produces only six stamens, the pollen-producing organs of the plant. Plants with a "Clark Kent" mutation have an excessive number of stamens that are easy to see with the naked eye. Jacobsen showed that the "Clark Kent" mutations were variants of "Superman" and that they caused heavier methylation, which disrupted normal gene activity.
Jacobsen and his team later cloned three additional genes, "Chromomethylase3," "Kryptonite" - so named, of course, because it weakens "Superman" and "Clark Kent" - and "Argonaute4." Each gene reveals more about the mechanism of methylation and the interaction of methylated DNA with modified histones, proteins that help wrap up the DNA into tightly packed chromosomes, as well as with small RNA molecules that target methylation.
Jacobsen received a Searle Scholar Award and a Beckman Young Investigator Award, and he was elected as a Fellow of the American Association for the Advancement of Science.
The Howard Hughes Medical Institute provides long-term, flexible funding to enable its investigators to pursue their scientific interests wherever they lead. The institute currently employs approximately 300 investigators from more than 60 such host institutions, along with more than 2,000 of their scientific staff.
"We are committed to providing these scientists - and the nearly 300 scientists who are already part of HHMI - with the freedom and flexibility they need in order to make lasting contributions to mankind," said Thomas R. Cech, the institute's president. "We want and expect them to be daring."
The new institute investigators are drawn from 31 institutions nationwide, representing traditional biomedical research disciplines, as well as engineering, physics, chemistry and computer science.
The Howard Hughes Medical Institute is dedicated to discovering and disseminating new knowledge in the basic life sciences. Founded in 1953 by the aviator-industrialist and headquartered in Chevy Chase, Md., the institute grounds its research programs on the conviction that scientists of exceptional talent and imagination will make fundamental contributions of lasting scientific value and benefit to mankind when given the resources, time and freedom to pursue challenging questions. The institute spent $573 million in support of biomedical research and $80 million for support of science education and other grants programs in fiscal 2004.