ASU scientist Roy Curtiss receives Lifetime Achievement Award

March 25, 2014

Roy Curtiss III, a scientist at the Biodesign Institute at Arizona State University, has been selected as the 2014 recipient of the Lifetime Achievement Award from the American Society for Microbiology (ASM).

“During his career, Roy Curtiss has had a profound impact on the discipline of microbiology,” said John Young, chair of the ASM Lifetime Achievement Award Selection Committee. “He was a pioneer at the start of the recombinant DNA era, developing safe E. coli strains that could be used for gene cloning. He has also uncovered novel aspects of bacterial pathogenesis, and used this information to develop attenuated Salmonella-based vaccines that are effective against a myriad of human pathogens.” portrait of ASU professor, Dr. Roy Curtiss Download Full Image

“Roy’s achievements and lifelong dedication to life science research, education and innovation are remarkable,” said Raymond DuBois, executive director of the Biodesign Institute. “His fundamental work on microbial pathogenesis, coupled with a passion to tackle the dire challenges of combatting infectious diseases in the developing world make him a stellar example of the translational research mission of the Biodesign Institute.”

Winners of ASM’s Lifetime Achievement Award are a small and select group; Curtiss is just the 20th member to receive the distinction. “I was stunned to be included in this group of awesome scientists,” said Curtiss, director of Biodesign’s Center for Infectious Diseases and Vaccinology and professor of Life Sciences in the School of Life Sciences at ASU.

Curtiss stresses that microorganisms have had a profound effect on his career, as well as on all earthly life. “We derive all of our energy from bacteria that invaded early cells maybe 2 billion years ago: the mitochondria. All photosynthesis is due to bacteria invading early plant cells,” he says.

Of course, microbes have a notorious dark side as well, accounting for a staggering 35 to 40 percent of all human deaths every year. Critical issues of human health, in the United States as well as the developing world, have been an ongoing preoccupation for Curtiss: “We have a horrible problem with antibiotic resistance, drug resistance in influenza and HIV – so developing vaccines to prevent those diseases is a major focus of my endeavors as I continue my life of research.”

ASU leader

Curtiss was drawn to ASU President Michael Crow’s vision of a New American University and a state-of-the-art research enterprise, the Biodesign Institute, which opened in 2004. Shortly after arriving at ASU, Curtiss received the largest grant of his career, a $14.8 million grant from the Grand Challenges in Global Health initiative, funded by the Bill and Melinda Gates Foundation. (The project was supplemented the following year with another $631,000.)

Curtiss has led an international research project to develop a new vaccine to be administered needle-free to newborns and infants to combat pneumonia, a leading cause of death, especially in the developing world. The single-dose, oral vaccine against bacterial pneumonia promises to outperform the existing injectable vaccine in terms of safety, affordability, ease of distribution and effectiveness. Preliminary studies have been successful, and moved the vaccine technology forward to human clinical trials.

In the Curtiss lab, orally deliverable vaccines for fish, poultry, swine, cattle and humans are now being developed to protect against a broad range of pathogenic invaders. These include: Streptococcus pneumoniae causing pneumonia, Mycobacterium tuberculosis causing tuberculosis, Yersinia pestis causing plague, human gut pathogens such as Salmonella, E. coli and Shigella, as well as influenza and hepatitis B viruses.

Curtiss has demonstrated the power of such vaccines to stimulate a robust immune response, conferring protective immunity to bacterial, viral and parasitic infectious disease agents. “It’s now become clear that we can use these microbes in other ways against diseases like inflammatory bowel disease, Crohn’s disease or even in therapies for cancers of different types – both lymphomas and solid tumors,” he says.

Backyard prodigy

Curtiss enjoys a reputation as a trailblazer for investigating the genetic basis of bacterial infection, and is recognized as one of the world’s outstanding figures in the field of vaccinology. His dramatic career began at an early age.

“One of the things that got me interested in biology and science was moving from New York City to Upstate New York, where we had a backyard and a place for a garden. My father taught me how to put seeds in the ground,” he recalls. “In the fall, I had a huge sunflower that I took to the Albany Flower Show and I won my first blue ribbon – at age 5.”

Soon, new questions began to intrigue the young scientist, sparking an early fascination with the genetics of vegetables like tomatoes and their resulting distinctive colors, and later, the inheritance of plumage colors in chickens. “I just kept asking questions, exploring new areas.”

After honing his skills in the breeding of chickens, Curtiss took first place in the New York State 4-H Chicken of Tomorrow contest in 1950. For his winning entry, he produced a White Cornish-White Plymouth Rock cross. The genetic background of this bird represents 95 percent of the chickens currently raised and consumed for food in the United States, something Curtiss takes great pride in. In later years, he would develop a broad range of vaccines to protect poultry and other animals from a variety of infectious diseases, particularly Salmonella infections in broilers and laying hens.

Under the microscope

In addition to talent and hard work, Curtiss attributes a long list of milestones in microbiology to his knack for being in the right place at the right time and fostering relationships that would shape his highly varied career.

Roy Curtiss III was born in New York, May 27, 1934. He became absorbed with microbiology in high school when he began testing for Salmonella in poultry. After graduation, he pursued his early fascinations more rigorously, researching the physiology of Salmonella and other bacteria, as well as entities that infect and replicate within bacterial host – known as bacteriophages (bacterial viruses).

Curtiss received his undergraduate degree in agriculture from Cornell University, Ithaca, N.Y., in 1956. There, he was a member of Quill and Dagger, a legendary collegiate senior honor society reserved for outstanding student leaders.

The early experience of attending the Cold Spring Harbor symposium in 1956 was a formative one for the young researcher. “That was the beginning of the era of molecular biology. The phage group had only 30 or 40 people. Six of these people went on to get Nobel prizes,” he says. “To be surrounded by a small group of eminent scientists exchanging ideas, arguing and discussing biology was just phenomenal.”

Curtiss went on to receive his doctorate in microbiology from the University of Chicago in 1962 and quickly advanced in leadership roles at a number of major American universities. At the University of Tennessee at Oak Ridge, Curtiss carried out a variety of roles from 1962 to 1972, including lecturer in Microbiology; interim director of the Graduate School of Biomedical Sciences; and group leader, Microbial Genetics and Radiation Microbiology Group, Biology Division. During this time, he also spent three years as an elected member of the Oak Ridge City Council.

From 1978-1983, Curtiss taught and conducted research at the University of Alabama-Birmingham, where he was Charles H. McCauley Professor of Microbiology; director of the Molecular Cell Biology Graduate Program; senior scientist in the Comprehensive Cancer Center; senior scientist in the Institute of Oral Biology; and founder and director of the Cystic Fibrosis Research Center (and acting chairman, Department of Microbiology in 1982).

Prior to his appointment in 2004 to ASU’s School of Life Sciences and the Biodesign Institute, Curtiss worked at Washington University in St. Louis, where he chaired the Biology Department for more than a decade, earning the title of George William and Irene Koechig Freiberg Professor of Biology in 1984.

Not done yet

Today, Curtiss marvels at the huge expansion of the field of microbiology since his early days. “It’s a much more complex society and enterprise we’re engaged in today. There are 40,000 members of the ASM, which is one of the largest biological science organizations in the world.”

Concerning Curtiss’ active role in the microbiology community, ASM Selection Committee chair Young adds, “Roy has performed exemplary service to ASM, serving as an effective spokesperson and promoting the field of microbiology on the international stage. He is also a renowned mentor, and has trained numerous talented young scientists who have gone on to become international leaders in their fields.”

In addition to recognizing Curtiss’ significant research contributions in many areas of microbiology, the ASM award acknowledges his lengthy list of major publications and numerous patents. Notwithstanding his superlative achievements, Curtiss shows no signs of slowing down. “My life isn't over yet ... and I’ve still got lots to do!”

A ceremony honoring Curtiss will take place at the ASM General Meeting Awards Banquet and Dinner on Sunday, May 18, in Boston, Mass. There, he will present the ASM Lifetime Achievement Award lecture.

Roy Curtiss is a member of the National Academy of Sciences and Fellow of the American Academy of Microbiology; the American Association for the Advancement of Science; the St. Louis Academy of Sciences; and the Arizona Arts, Science and Technology Academy.

Richard Harth

Science writer, Biodesign Institute at ASU

480-727-0378 richard.harth@asu.edu

Innovative technique provides inexpensive, rapid, detailed analysis of proteins

portrait of ASU researcher Dr. Paul Oran

At ASU's Biodesign Institute, research focuses on the analysis of proteins using mass spectrometry – a powerful tool for the detailed investigation of protein structure.

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Innovative technique provides inexpensive, rapid, detailed analysis of proteins

March 25, 2014

Proteins are vital participants in virtually all life processes, including growth, repair and signaling in cells; catalysis of chemical reactions and defense against infection. For these reasons, proteins can provide critical signposts of health and disease, provided they can be identified and assessed in a clinical setting.

Accurately characterizing proteins for diagnostic and therapeutic purposes has been an enormous challenge for the medical community. At the Biodesign Institute’s Molecular Biomarkers Laboratory at Arizona State University, research focuses on the analysis of proteins using mass spectrometry – a powerful tool for the detailed investigation of protein structure. portrait of ASU researcher Dr. Paul Oran Download Full Image

The facility is under the direction of Randy Nelson, a pioneer in the field and developer of Mass Spectrometric Immunoassay (MSIA), a high-throughput protein quantification technique that also provides detailed protein information, including post-translation modifications and genetic variants. Currently, the research group is focused on developing and translating new assays for protein biomarkers related to cancer, diabetes and heart disease.

In a new study appearing in the journal PLOS ONE, lead author Paul Oran and his colleagues demonstrate the power of MSIA platform, with a vision toward clinical adoption. The research reports a high-throughput method for quantifying and characterizing insulin-like growth factor 1 (or IGF1) at a rate of >1,000 human samples a day. IGF1 is a critical protein implicated in human growth disorders, as well as certain forms of cancer.

Insulin-like growth factor 1 is a 70-amino acid protein involved in cell growth, differentiation and transformation. Most IGF1 is secreted by the liver and acts as an endocrine hormone.

“For several decades, researchers have struggled to accurately quantify IGF1, an important molecule used to diagnose different kinds of growth disorders,” Oran says.

In addition to providing a mass spectrometry-based IGF1 assay capable of being used clinically someday, the new research reports – for the first time – how efficient and cost-effective the technique can be. In their study, they were able to analyze over 1,000 samples in a single day (a milestone needed for eventual clinical use).

“From our knowledge, this is the first demonstration of an MS-based, targeted-proteomics assay for IGF1 – or any protein for that matter – capable of running at this speed and cost,” says Oran.

Mass spectroscopy can readily identify genetic variants that are expressed on the protein level (for example, Single-nucleotide polymorphisms). Such changes may alter or disable the function of the resulting protein. Further, mass spectroscopy can pinpoint changes that may occur to the protein after it has already been produced from the gene template – so-called post-translational modifications.

The complex picture of multiple variants of a given gene coupled with post-translational protein alterations is referred to as microheterogeneity. Resulting protein variants play a major role in a variety of diseases, yet their identification has been fraught with difficulty. The current clinical standard for many types of protein quantification has been a method known as ELISA (enzyme-linked immunosorbent assay).

Mass spectroscopy, however, is able to analyze critical protein variants, wheras ELISAs cannot. Microheterogeneity can also produce interference in ELISA tests, causing them to mechanically fail, yielding false readouts. Analysis through mass spectroscopy fixes the interference problem, additionally producing a rich portrait of protein information not available to ELISA. “As we and others have seen repeatedly, microheterogeneity is linked to many forms of disease,” Oran says.

A mass spectrometer is an analytical instrument capable of producing spectra of the molecular masses of molecules contained in a sample. Once a sample is ready to be analyzed on a mass spectrometer, a protein and its variants can then be separated and categorized by their unique mass-to-charge ratio, which provides a sort of molecular fingerprint.

In the case under study in the current paper, IGF1 molecules detected in blood are usually bound with two other proteins. “To accurately quantify this molecule, we have to first disrupt this complex so we can get an accurate readout of total IGF1,” Oran says.

The platform described in the current study is a so-called “top-down” approach to protein quantification. Instead of digesting the protein by means of proteases like trypsin and extracting the resulting tiny peptide fragments for analysis by mass spectroscopy (“bottom-up”), a top-down method captures a full-length protein and any protein variants in their entirety, enabling rapid analysis of a protein and its variants.

“Other competing bottom-up approaches struggle to identify and thus, ignore microheterogeneity, cost substantially more and require more time and labor per sample,” Oran says.

In the current study, the group quantified 1,054 human samples in nine hours – a throughput rate on a par with ELISA – while providing more detailed information on the IGF1 protein, available only through mass spectroscopy. The new method also detected mutations in roughly 1 percent of the samples tested.

Future research will entail a larger validation study intended to support clinical adoption of the assay. The large universe of human proteins provides a broad range of plausible diagnostic targets. Several dozen assays using the technology have already been developed in Nelson’s lab.

“From our knowledge, this is really the first viable option for routine analysis in a clinical laboratory that meets cost and time requirements while taking advantage of mass spectroscopy to quantify proteins,” Oran says.