Member SpotlightsThe Ward Group at Rutgers University Finds New Ways to Use GFP in Biomedical Diagnostics William W. Ward, Ph.D. A Science Advisory Board Member Since 2003  William W. Ward, Ph.D., of Rutgers University & Brighter Ideas, Inc. Academic Background and Current Research Interests Dr. William W. Ward has been on the faculty of Rutgers University in New Brunswick, N.J., since 1977 where he is currently Associate Professor of Biochemistry and President and CEO of the biotechnology company Brighter Ideas, Inc. Professor Ward received his BS and MS degrees from the University of Florida and, funded by a nationally competitive NSF pre-doctoral fellowship, received a Ph.D. in biology from Johns Hopkins University in 1974. His graduate work under Dr. Howard Seliger led to five major refereed publications in the field of marine bioluminescence, including seminal papers on the calcium-triggered luminescence systems of the comb jellies, Mnemiopsis and Beroe. His action spectrum for photoinactivation of the calcium-triggered photoprotein, mnemiopsin, a spectrum that demonstrates sensitized destruction of luminescence potential via photoexcitation of the bound luciferin molecule, is one of the most precise action spectra on record. He then traveled to Athens, Georgia, where he worked as a post-doctoral research associate in the University of Georgia’s Department of Biochemistry under Dr. Milton Cormier. Supported there with a nationally competitive NIH post-doctoral fellowship, Dr. Ward initiated his career-spanning research on green-fluorescent protein (GFP). His 1979 paper in the Journal of Biological Chemistry 254:781-788, “An Energy Transfer Protein in Coelenterate Bioluminescence: Characterization of the Renilla Green-Fluorescent Protein (GFP),” remains, to this day, one of the most comprehensive characterizations of any fluorescent protein. In this and related papers, he showed that Renilla luciferase forms a reversible energy transfer complex with Renilla GFP, so as to generate green (rather than blue) bioluminescence, in vitro. This electrostatically stabilized protein-protein interaction complex is so specific, that cross-reactions occur among species of the same genus, but rarely among more distantly related sea pansies and sea pens. He was the first to show that the protein-bound light-emitting chromophores in the calcium-triggered photoproteins, aequorin, mnemiopsin, and berovin are identical to Renilla luciferin (coelenterazine) and proposed that the chromophores are covalently attached to their respective proteins via reducible endoperoxide linkages. His research in the Cormier lab led to nine refereed publications and a half dozen published abstracts. In 1977, Dr. Ward was appointed to the faculty of Biochemistry and Microbiology at Rutgers University on the Cook College Campus in New Brunswick. His major research accomplishments at Rutgers include contributions leading to the elucidation of the chemical structure of the Aequorea GFP chromopeptide, the primary sequence of Aequorea GFP, and the first cell-free synthesis of GFP. His group demonstrated the oxygen dependency for GFP maturation, the susceptibility of Aequorea GFP to external perturbations, the reversibility of GFP denaturation, and the ability of genetic color variants of Aequorea GFP to form reversible heterodimers. He contributed to the February 11, 1994, cover story (Science 263:802-805), “Green Fluorescent Protein as a Marker for Gene Expression,” that announced the first successful cloning of a fluorescent protein in a heterologous organism -- a paper that quickly grew to be among the ten most cited papers in all of biotechnology. Dr. Ward conceived of, organized, and fully administered three international symposia on GFP (1997, 1999, and 2004). He is frequently asked to speak at national and international symposia and conferences and has authored or co-authored 28 books and book chapters, 25 refereed journal articles, and 65 published abstracts. He has filed 8 patent applications, two of which have been issued. Professor Ward is one of the most experienced and dedicated teachers at Rutgers University, voluntarily taking on heavier than normal teaching loads each semester in undergraduate, graduate, and continuing professional education programs. His academic center, CREBB (Center for Research and Education in Bioluminescence and Biotechnology), offers internationally recognized hands-on short course training programs for biopharmaceutical and life science professionals. The center training program has been running continuously for more than 20 years, training 1500 scientists from all corners of the globe while raising more than $2 million. Each year, he mentors up to 20 undergraduate students in supervised research and research honors programs. In 1996, he received a prestigious NSF-ATE grant ($350,000) to develop GFP-based teaching modules for high school and college level laboratory biotechnology courses. This grant helped launch the highly successful Biotechnology Explorer series of instructional kits manufactured and distributed by BioRad Laboratories. The cloning of Aequorea GFP in 1994 was a career-altering milestone for Professor Ward. Shortly after this breakthrough Science paper, his program began to take on a new focus, moving from traditional, basic academic research and teaching toward commercial applications of GFP. There are now 10 companies who rely upon Dr. Ward’s center, CREBB, and his newly formed company, Brighter Ideas, Inc., to supply them with highly purified recombinant GFP (expression and purification services) and purified polyclonal antibodies generated in rabbits and chickens to native jellyfish GFP. Annually, these ventures raise up to $500,000 of combined revenue for CREBB and Bii. What early motivations contributed to your current research interests? In 9th grade, I took the Kuder Preference Test, a career-predictive exam that revealed, in my case, two dominant interests -- scientific and artistic. I was not surprised to learn of my scientific inclinations, as I had always been interested in science, but the artistic interest revealed by the test, was unexpected. In retrospect, however, I see artistic leanings in everything I have done. My life-long odyssey has simultaneously followed scientific and artistic paths. I was attracted to the field of bioluminescence as a master’s student, primarily for aesthetic reasons. Over the years, my appreciation of the beauty of biological light has only intensified. From early elementary grades through later college years, I engaged in a variety of school-related artistic ventures. Beginning in 4th grade, I developed an artistic interest in geography, constructing dozens of elaborate flour and salt relief maps, many of which consumed more than 100 hours to design and build. As an excuse for not being a very good language student, I built 15 or 20 working miniature models of Roman weapons, from scratch, simply by studying pictures of these devices in my high school Latin book. Despite never taking an art course, the biology drawings I created were always the best among my peers in every biosciences course I took in high school and college. So focused was I with drawing that I seriously considered going into medical illustration as a career. In college humanities class, I volunteered to create a detailed drawing of the Acropolis for my professor to use in a class quiz. My attention was so riveted to this artistic “gig” that, at quiz time, I was unable to identify two of the ten architectural structures I had spent so much time drawing. In my mid 40’s, never having had voice lessons, I began performing in a Unitarian Church choir. Before long, I was on stage, performing in community operettas -- first “Ahmal and the Night Visitors” and, later, Gilbert and Sullivan’s, “The Sorcerer,” “Trial by Jury,” “The Mikado,” and “Pirates of Penzance,” (where I met my wife of 16 years). Soon, I was doing “Hair,” “Mame,” “Carousel,” “Baby,” “Kiss Me Kate,” “Babes in Arms,” and “Fiddler on the Roof” (twice). At about the same time I began phasing out musical theatre “gigs,” in 2000, I found myself writing satires. In the past 7 years, now under contract with a book publishing company, Jones Harvest Publishers, I have written or drafted six satires. The titles include: “Hey, Doc! Does Speling Count?” “I’m a Bush-Republican Because -- the 72 Best Reasons,” “Why Do They Jog When They’ve Nothing That Jiggles?” “America’s 43rd Best President,” “Snake Oil, Revisited,” and “Turn Right To Go Left.” In my 17 seasons of jellyfish collecting in Friday Harbor, WA, I noticed, once in a while, that a jellyfish dropped on a paper towel would partially dry overnight, leaving an attractive imprint upon that towel. Season after season, I worked on a procedure that would leave a near-perfect imprint of the jellyfish, finally selecting high quality glass-fiber paper to make my imprints. This has evolved into an interesting wall-hanging art project, Marine Impressions. I now have more than 80 dried, preserved, and artistically stained jellyfish prints in the collection -- no two alike in appearance. What was the most memorable turning point in your career? As unlikely as it may seem, the greatest turning point in my career was having failed French in my senior year of college. A Biology major with no clue what I wanted to do with the degree, but facing the draft along with most other young men, I decided at the end of my junior year to enlist in Naval Officer Candidate School as a prospective US Naval pilot. At Navy expense, I was flown from Gainesville to Jacksonville, Florida, in an Electra prop jet (my first airplane ride) to take the written and physical tests for OCS, both of which I passed. But, my failing French the next semester forced postponement of my college graduation date from 1964 to 1965. The Navy required that I retake my OCS exams in order to stay in the program, but, by late 1964, the Vietnam War had so intensified that I no longer wanted any part of a military career. So, graduate school it was. Tell us about your most recent professional activities. In 2001, my colleague, Dr. Gavin Swiatek, and I made a discovery that led to the 2003 filing of a Rutgers University patent application for a novel biomedical assay for proteases and protease inhibitors. Called “GFP-on-a-String,” this high throughput screening assay quantitatively measures unknown or modified proteases, comparing the substrate specificity of any unknown with an extensive electronic database of knowns. As a vehicle to develop “GFP-on-a-String,” Brighter Ideas, Inc., was incorporated in 2003. The patent, that was issued on February 12, 2008, is licensed exclusively by Rutgers University to Brighter Ideas. Bii also holds the exclusive license from Rutgers to develop a second W.W.Ward invention, a protein extraction and purification kit, tentatively called “The Green Gene Screen.” In 30 minutes (either on the micro-scale or commercial macro-scale), the GGS kit semi-selectively isolates a protein-of-interest from whole, unlysed cells and purifies that protein up to 100-fold with respect to other proteins in the cells. Everything is accomplished with readily available equipment. While greatly reducing sample viscosity and turbidity, the GGS kit concentrates the sample 50-fold or more, removing virtually all cell debris, cytoplasmic DNA, lipids, pigments, and other small molecule contaminants. In my 40 years as a protein biochemist, I have found no batch purification method as effective and efficient as GGS. In addition to serving as a biomedical assay and “tool” company, Brighter Ideas, Inc. is a leading provider of purified polyclonal antibodies raised in rabbits and chickens to native jellyfish GFP. We also offer custom expression and purification services for a variety of cloned fluorescent proteins and we provide expert training and consulting services in molecular cloning and gene-product purification. To help us develop a portion of our IP portfolio, Bii has entered into several strategic partnerships with innovative companies. We continue to offer exciting opportunities for others to partner with Brighter Ideas, Inc., or to invest in our “bright” future. To discuss green fluorescent protein (GFP) technology and other topics with fellow Science Adivisory Board members, please visit our community forum. The following are web links mentioned in this article:. CREBB (Center for Research and Education in Bioluminescence and Biotechnology) Marine Impressions Brighter Ideas, Inc. ### << Previous Next >> [ View All Member Spotlights ] |
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