Environmental Factor, April 2011, National Institute of Environmental Health Sciences
University of Washington trainee headed to Lindau
By Eddy Ball
"It was my interest in this enzyme that took me to Seattle at the end of 2009 [to work with] Dr. Furlong, who is one of the top scientists studying PON1," said Marsillach Lopez, shown here in the bleachers above the UW Husky stadium. (Photo courtesy of Judit Marsillach Lopez)
Furlong said of his protégée, "Judit is an outstanding young scientist, and I'm certain she'll return to Seattle overflowing with new perspectives on science and society. This program certainly represents a wise investment in the next generation of leading scientists." (Photo courtesy of Clement Furlong and the University of Washington)
With sponsorship by her home State of Catalonia, Spain, trainee Judit Marsillach Lopez, Ph.D., will attend the prestigious Lindau Nobel Laureate Meeting(http://www.lindau-nobel.org/meeting/) June 26-July 1 in Germany. A fellow at the University of Washington (UW), Marsillach Lopez receives research support from NIEHS and holds a Beatriu de Pinós Postdoctoral Fellowship(http://www10.gencat.cat/agaur_web/AppJava/english/a_beca.jsp?categoria=postdoctorals&id_beca=17221) from the government of Catalonia, an autonomous region of Spain.
This summer, Marsillach Lopez will join approximately 25 Nobel laureates in physiology or medicine and some 550 other outstanding young researchers from throughout the world in a series of lectures, discussion sessions, and other activities designed to foster inter-generational scientific discourse.
"I am honored by my selection," Marsillach Lopez said of the upcoming meeting, "and I am proud to be representing the people of Catalunya [Spanish for Catalonia] at this international event."
NIEHS support for genetic research
Marsillach Lopez is a member of the UW lab headed by Clement Furlong, Ph.D.(http://www.gs.washington.edu/faculty/furlong.htm) , professor of genome sciences and of medicine in the Division of Medical Genetics. The group studies the genetic variability of insecticide metabolism and sensitivity in humans. Marsillach Lopez' research on paraoxonase (PON1), a high-density lipoprotein (HDL)-associated enzyme that inactivates the toxic metabolites of several organophosphate pesticides (OP) and nerve agents (see text box), has received support from three NIEHS grants to UW:
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- Structure and Function of the Human PON1 Polymorphism(http://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=R01ES009883) - Furlong, principal investigator (PI)
- Superfund Research Program Effects-Related Biomarkers of Environmental Neurotoxic Exposures(http://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=P42ES004696) - Harvey Checkoway, Ph.D., PI
- Center for Child Environmental Health Risks Research(http://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=P01ES009601) - Elaine Faustman, Ph.D., PI
What promises to be a week to remember
As one of what the Lindau organizers describe as "international Best Talents," Marsillach Lopez will participate in an activity-filled week of social and intellectual interaction among laureates and students living, eating, and talking together in and around the historic island city of Lindau. The city sits on the shore of Lake Constance, the Bodensee, where the borders of Germany, Austria, and Switzerland meet.
The Lindau meetings began in 1951 as a sort of reunion for expatriate German scientists who left their country during the Nazi period. From the outset, organizers envisioned the meeting as a nonideological gathering of inquiring minds dedicated to transferring knowledge between generations.
Understanding host response to environmental exposures
The Furlong lab studies the molecular basis of the genetic polymorphism in human plasma paraoxonase 1 (PON1) that specifies high or low metabolism of organophosphate (OP) insecticides and nerve agents. Low levels of this enzyme are also a risk factor for cardiovascular disease.
Since joining the Furlong group, Marsillach Lopez has worked on several NIEHS-funded projects. One of the first projects is focused on characterizing biomarkers of exposure to OP insecticides. Her group successfully developed rapid immunomagnetic bead protocols for purifying biomarkers that are modified by OP exposure, butyrylcholinesterase (BChE) and acylpeptide hydrolase (APH). Using mass spectrometry, the team identified specific adducts to the active-site serines in these proteins.
Another project is related to the structure and function of human PON1 and producing recombinant variants of PON1 to better understand the function of this multi-tasking enzyme. One goal of these studies is to generate recombinant PON1 molecules with much higher catalytic efficiencies of OP hydrolysis that can be used to treat cases of OP poisoning, such as nerve agent exposure and exposure to OP insecticides for which the catalytic efficiency of the native PON1 is too low to protect a person from the exposure.
Furlong's group is also generating variants of human PON1 that have been associated with amyotrophic lateral sclerosis (ALS) - Lou Gehrig's disease - to better understand the properties of the variant proteins. To that end, the researchers are striving to improve purification protocols for PON1. Using anti-PON1 antibodies generated in rabbits, they have been able to purify PON1-containing HDL particles in a single step. These protocols will allow them to examine the proteomics of PON1-containing HDL from healthy and diseased individuals and better understand the role of PON1 in diseases such as cardiovascular disease and ALS.