Research Interests
My lab is conducting two distinct research projects. In the first project,
we are investigating the mechanisms that control the uptake and homeostasis
of iron. This project has important implications both for our basic understanding
of these mechanisms, and also for our ability to manipulate the iron content
of particular plant parts as a means of improving the iron nutritional
quality of food. In the second project, we are using molecular approaches
to discover genes involved in production of paclitaxel (generic name for
Taxol™ - Bristol-Myers Squibb). Genes discovered during this project
will improve our ability to supply sufficient quantities of paclitaxel
to the world.
Iron uptake and homeostasis
We recently identified and cloned a transposon-tagged allele of the maize
gene, yellow stripe1 (ys1). The product of ys1 mediates
iron uptake in grass species, a process that is of fundamental importance
for understanding and manipulating iron homeostasis in the world's major
grain crops. Grasses have solved the problem of limited bioavailability
of iron using a strategy that is fundamentally different from the mechanisms
used by other plant groups. Grasses secrete "phytosiderophores": non-proteinogenic
amino acid derivatives that form stable Fe[III] chelates. YS1 is the transporter
that is located at the root surface and specifically recognizes and takes
up the Fe[III].phytosiderophore complexes, which are the plant's source
of iron. With cloning of ys1, transfer of more efficient iron uptake
into non-grass species becomes possible, allowing better growth in calcareous
soils, and better iron nutritional quality in edible parts.
Another surprising but important discovery is that genes with strong
sequence similarity to ys1 are found in non-grass species (monocot,
dicot, gymnosperm, and moss species) that neither synthesize nor have
the ability to use phytosiderophores. All these species do, however, contain
a related compound, nicotianamine, an iron chelator that is structurally
similar to phytosiderophores. Nicotianamine appears to have several roles
in plants, all of which relate to allocation of transition metals in plant
cells and organs. Nicotianamine-metal chelates are likely to be transported
across cell membranes by YS1-like (YSL) proteins, thus by understanding
the locations and timing of expression of these transporters we will gain
new insight into the patterns of long range metal ion movement in plants,
which is poorly understood at present. Much of our current effort is aimed
at the functional genomics of the Yellowstripe-like (YSL) family
of genes in Arabidopsis thaliana, a model system in which we can
answer these and many other questions. For more information about this
project, please visit our 2010
web site.
Paclitaxel biosynthesis
We are using molecular approaches to delineate
global metabolic control of paclitaxel accumulation in Taxus cell cultures. Paclitaxel
(generic name for Taxol™ - Bristol-Myers Squibb) has been approved by the Food and Drug
Administration (FDA) for the treatment of breast, ovarian and lung cancers as well as the
AIDS-related Kaposi's sarcoma. The original supply of paclitaxel was obtained through the
extraction of yew tissue (the largest proportion of paclitaxel is found in the bark of
the yew). However, the yew tree is slow-growing with low paclitaxel yields. Because two
to four mature trees are needed to supply enough paclitaxel for the treatment of one patient,
supply of paclitaxel from natural sources was limiting, and alternative methods of
production such as cell culture systems for production are actively sought. We are using
transcription profiling to identify genes involved in global metabolic control. Such genes
will be involved not just in paclitaxel biosynthesis (where all current efforts are focused),
but also in transcriptional regulation, transport, secretion and degradation.
|
Representative Publications
DiDonato, R. J., Roberts, L. A., Sanderson, T., Eisley, R. B.
and Walker, E. L. 2004. Arabidopsis Yellow Stripe-Like2 (YSL2):
a metal-regulated gene encoding a plasma membrane transporter of
nicotianamine-metal complexes. The Plant Journal, 39: 404-413.
Roberts, L. A., Pierson, A. J., Panaviene, Z., and Walker, E. L. 2004.
Yellow Stripe1. Expanded Roles for the Maize Iron-Phytosiderophore Transporter," Plant
Physiology, 135: 112-120.
Curie,C., Panaviene, Z., Loulergue, C., Dellaporta,, S. L., Briat, J-F.,
and Walker, E. L. 2001. Maize yellow stripe 1 encodes a
membrane protein directly involved in Fe(III) uptake. Nature,
409: 346-349.
Walker, E. L. and Panavas, T. 2001. Molecular analysis of r1
geographic haplotypes: structural and epigenetic features associated with
activity in paramutation. Genetics, 159: 1201-1215.
Bercury, S. D., Panavas, T., Irenze, K., and Walker, E. L. 2001. Molecular
analysis of the Doppia transposable element of maize. Plant
Molecular Biology, 47: 341-351.
Panavas, T., Weir, J., and Walker, E. L. 1999. The structure and paramutagenicity
of the R-marbled haplotype of Zea mays. Genetics,
153: 979-991.
Panavas, T., Pikula, A., Reid, P. D., Rubinstein, B., and E. L. Walker
1999. Identification of senescence-associated genes from daylily petals.
Plant Molecular Biology, 40: 237-248.
Panavas, T., Walker, E. L., and B. Rubinstein 1998. The role of ABA in
programmed cell death of daylily petals. J. Exp. Bot., 49:
1987-1997.
Walker, E.L. 1998. Paramutation of the r1 locus of maize is associated
with increased cytosine methylation. Genetics, 148: 1973-1981.
|
