Winter 2008/09

In this issue

ISS Transits the Sun

Astrophotographer Jerry Lodriguss caught this dramatic image on July 8, 2007.  Additional astronomical photographs, as well as tips for digital astrophotography and image processing, may be viewed at his website.

ISS transits across the face of the sun.

The International Space Station (ISS), with its new solar arrays, transits across the face of the sun. 
Sunspot group 963 is also visible on the eastern limb of the Sun, just rotating on.

Space Radiation Spotlight on William F. Morgan

William F. MorganWilliam F. (Bill) Morgan was born and raised in New Zealand, with two two-year sojourns in Malaysia while his father was part of the British commonwealth forces stationed there during the Indonesian confrontation.  In 1977 he completed a B.Sc. in botany at the University of Canterbury in Christchurch, followed by a M.Sc. and a Ph.D. in cytogentetics at the same institution.  While working at Christchurch Hospital, he did graduate work investigating the frequency and distribution of sister chromatid exchanges (SCE’s) in human chromosomes.  After graduation, an opportunity beckoned him to migrate to the USA in 1981 to join Prof. Sheldon (Shelly) Wolff, one of the pioneers of the SCE technique for postdoctoral studies at the Laboratory of Radiobiology & Environmental Health at the University of California, San Francisco (UCSF).

He joined a research team at UCSF that included Harvey Patt, Bob Painter, Roger Pedersen, Zena Werb, Michael Banda and Jim Cleaver as senior faculty and postdoctoral colleagues Jeff Schwartz, John Murnane, Bill Kauffman, Jean Bennet, Dieter Gruenert amongst others.  While enjoying the many charms and attractions of San Francisco, this merry group made time to investigate the mechanisms and significance of SCE formation, the adaptive response to low doses of ionizing radiation, and the role of poly ADP (ribosylation) in cellular responses to DNA damaging agents.

Promoted to Assistant Professor in 1984 and with Shelly’s support and encouragement, he began to establish an independent research career. The goal of the lab was to understand the mechanisms of how and why chromosomes rearrange after exposure to DNA damaging agents. It was a particularly exciting time as this was the beginning of the molecular biology revolution.  With funding from the Department of Energy (DOE), the Morgan laboratory developed techniques for introducing restriction endonucleases into cells in order to understand how a DNA double strand break could lead to SCEs and/or chromosomal rearrangements.  Introducing an endonuclease either on a plasmid vector or by electroporation enabled them to investigate the biological consequences of introducing a defined lesion, a double strand break at a known DNA sequence in the genetic material.  Understanding cellular responses to induced DNA double strand breaks occupied the Morgan laboratory for many years. A number of outstanding technical staff, students, postdoctoral research fellows, and visiting scientists joined in this endeavor.  These included Felipe Cortes, Hai-won Chung, Krishan Saxena, Melisa Molero, Richard Winegar, Jeff King, Elma Abella-Columna, Barbara Yates, Eva McGee, Joe Day, Jim Carney, Brian Ponnaiya, Mark Kaplan, Matt Fero, Joan Rufer, Kate Land, Brad Marder, Cecelia Fairley and John Phillips. 

However, it was John Phillips’ father, Theodore (Ted) Phillips, chairman of the Department of Radiation Oncology at UCSF who transformed Morgan’s scientific interests.  Restriction enzyme-induced DNA double strand breaks were a superb mimic of the primary lethal lesion induced by ionizing radiation. Hence, understanding how cells respond to induced breaks could well provide important clues to understanding the detrimental effects of ionizing radiations.  Ted offered Morgan a joint appointment in the Department of Radiation Oncology, and thus a clinical “home.”  Shortly after this appointment however, Bill Dewey and other senior members of the Department either relocated or went on sabbatical leaving the residents without a radiation biology tutor.  Since the best way to learn a subject is to teach it, Morgan and John Fike, soon were translating Eric Hall’s book Radiobiology for the Radiologist to the residents and interested graduate students.  Thus Morgan’s interest in radiation biology was born and nurtured.

Things in the lab were going extremely well. There was an active program in understanding the molecular mechanisms of DNA double strand break repair and an exciting developing program in radiation-induced genomic instability. In trying to isolate clones of hamster human hybrid cells containing stable chromosomal translocations, Brad Marder and Morgan observed that radiation could induce genomic alterations in the progeny of irradiated cells long after the initial exposure. This phenotype was initially described by Munira Kadhim, Eric Wright and colleagues, and when Charles (Charlie) Limoli joined the lab as a bone fide radiobiologist, his enthusiasm stimulated other fellows and students including Andreas Hartmann, Mark Kaplan, and James Corcoran to develop and mature this program. This program was funded in large part by a joint NASA, NIH award. The lab was extremely productive, and these were exciting times!

It became clear that understanding the mechanisms of chromosomal rearrangements would require a combination of their molecular and cellular analysis with biochemistry to determine how DNA double strand breaks lead to complex cytogenetic aberrations.  The recruitment of postdoctoral fellows Jim Carney and Angel Islas and a very productive and rewarding collaboration with John Petrini, now at Memorial Sloan Kettering Cancer Center, led to the identification of the genetic defect in the radiation sensitive disorder Nijmegen Breakage Syndrome.

Unfortunately the late 1990’s was a tough time in the radiation sciences – a significant valley in the cycles of peaks and valleys in funding for basic research.  Due to fiscal constraints the DOE research budget was dramatically reduced, and the Laboratory of Radiobiology and Environmental Health at UCSF was closed, as were the radiobiology programs at a number of the national laboratories.  While the faculty eventually found new homes, Morgan was extremely fortunate that the DOE continued support of his research program, stipulating that he relocate that portion of his program to the Lawrence Berkeley National Laboratory (LBNL).  This relocation became his first introduction to the space radiation program.  He joined Aloke Chatterjee, Pricilla Cooper, Amy Kronenberg, Ellie Blakeley, Bjorn Rydberg, Mary Helen Barcellos-Hoff and colleagues to discuss progress on their NASA NSCORT program with Colorado State University.  LBNL was interesting and entertaining.  Furthermore, it provided him the opportunity to focus his research program that was becoming more ambitious (unwieldy) and outgrowing the space available at UCSF.  Top notch personnel in the Berkeley laboratory, like Jeff King, Jim Carney, Cecelia Fairley and Angel Islas, ran the “repair” program when it moved to Berkeley, while Charlie took care of the “instability” program that remained at UCSF.

Morgan’s interest in the effects of high Z radiations came from being at LBNL and from an RFA from NASA and NIH requesting applications to investigate potential delayed effects induced by radiations commonly encountered in space.  Morgan’s lab received funding from this initiative. Thus, he and Charlie made the first of many trips to Brookhaven National Laboratory (BNL) where they visited old friends like Dick Setlow, Carl Anderson, as well as Betsy and John Sutherland.  They interacted with Marcelo Vazquez and his colleagues in the Biology and Medical Departments and the wonderful Physics team – especially Jack Miller from LBNL.  Cosmic galactic radiations pose unique and interesting challenges to the radiobiologist and the issues of risk for the astronauts remain significant.

A conspiracy and convergence of a number of factors (that included the closing of the UCSF lab, commuting, Ted Phillip’s retirement, and the relocation of the LBNL lab) caused Morgan to look to the East for new opportunities.  Late in 1999 he and his family moved to the Department of Radiation Oncology at the University of Maryland, Medical School in Baltimore, Maryland.  He was grateful that Jim Carney agreed to relocate with him as a new Assistant Professor and his longtime friend, colleague and technician Jim (Corky) Corcoran came along as well.  Without Corky this move and their subsequent successes in Maryland would not have been possible, and Morgan acknowledge owing Jim an enormous debt of gratitude.

The chairman, Carl Mansfield, and vice chair Mohan Suntha, went out of their way to give Morgan’s group a warm welcome, and the atmosphere the chairs promoted at the University of Maryland fostered interaction and collaboration.  They were able to recruit Alan Tomkinson, a senior investigator in the DNA ligase field; Theresa Wilson, an expert in DNA mismatch repair; and Fey Rassool, whose interests were in radiation induced leukemogenesis to join incumbents George Harrison, Elizabeth Balcer- Kubiczek, Juong Rhee, and Tom MacVittie. Highly motivated new graduate students with innovative ways of looking at things: Shruti Nagar, Lei Huang, Andy Snyder, Lia Laiakis, Grace Kim, and Umut Aypar joined the team. The Radiation Oncology Research Laboratory thrived, and under the leadership of a new chairman, Bill Regine, the lab was ranked sixth nationwide in NIH funding in 2006.  However, Morgan considered his most significant achievement however to be convincing another Westerner to travel East.  He convinced Janet Baulch of the University of California, Davis to assume responsibility for the day-to-day operation of the lab, and particularly the NASA/BNL/NSRL program.  Janet has effectively run the lab’s space radiation program since she arrived in Baltimore. He is also proud to note that three of UM Baltimore students and postdoctoral fellows, Jarek Dziegielewski, Yujun Li and Umut Aypar have participated in the NASA Space Radiation Summer School.

In 2008 the opportunity to move to the Pacific Northwest National Laboratory (PNNL) presented itself.  Fueled in no small part by the fact that his wife Marianne Sowa lives and works there and by the opportunity to become part of the new DOE initiative on “Systems Radiation Biology,” Morgan moved to Richland, Washington in August 2008.  This has proven to be an opportunity to improve radiation risk prediction by linking mechanisms of cellular and molecular processing of radiation induced damage to macroscopic response processes at the tissue, organ and organism levels.  Traditionally radiation research has been a qualitative science in which parts of the process are studied individually by individual investigators.  However, systems biology is enabling a transition from this qualitative science to a quantitative, and ultimately predictive, science. This transition was made possible by advances in technology that have created a wealth of new information revealing the enormous complexity underlying biological processes.  His goal is to apply these systems approaches to both low LET radiations as well as radiations commonly encountered in space.

Throughout his career, Morgan has served on numerous (and on an eclectic variety of) study sections and committees.  In addition to “ad hocking” as a member of Paul Strudler’s Radiation Study Section, he served as a member of NCI Scientific Review Group Subcommittee C, from 1998 until 2003 and as chairman of that subcommittee from 2001 – 2003.  He has served time on review committees for NASA (Information Dynamics intermittently from 1995 – present); the Breast Cancer Research Program (BCRP), United States Army Medical Research and Material Command; the International Science Foundation; DOE’s Office of Health and Environmental Research; the National Sciences and Engineering Research Council of Canada; the University of California Energy Research Group; the March of Dimes; the UK’s Leukaemia Research Fund Radiation Leukaemogenesis Program and Medical Research Council; Singapore National University and Hong Kong University grants; as well as the DOE’s US Scientific Review Group for the Russian health Studies Program.  He is also a member of a member of the National Council on Radiation Protection, the International Commission on Radiation Protection (ICRP), and has served as a consultant to the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR).

The highlights of Bill Morgan’s career (above) have emphasized his successes, but he is quick to admit that none of his achievements would have been possible without the support of his parents Bill and Ngaire Morgan, his first wife and good friend Rosemary Wong, their children Michelle and Nick, and his second wife Marianne Sowa and her daughter Leyla.  To all of them he acknowledges a tremendous debt of gratitude and credits them with his current achievements.  He also extends his thanks, gratitude, and respect to his mentors Peter Fitzgerald, Peter Crossen, Jim Cleaver, and the late Shelly Wolff.  Last but not least, he acknowledges his many friends, collaborators and colleagues his these endeavors, without whom none of this would have been possible.

Selected Publications Since 1998

Carney, J.P., Maser, R.S., Olivares, H., Davis, E.M., LeBeau, M. Yates, J.R., Hays, L., Morgan, W.F. and Petrini J.H.J.  The hMre11/hRad50 protein complex and Nijmegen breakage syndrome:  Linkage of double-strand break repair to the cellular DNA damage response.  Cell 93, 477-486 (1998)

King, J., Fairley, C. and Morgan, W.F.  The joining of blunt DNA ends to 3’-protruding single strands in Escherichia coli.  Nucleic Acid Res. 26, 1749-1754 (1998)

Limoli, C.L., Hartmann, A., Shephard, L., Yang, C-R., Boothman, D.A., Bartholomew, J. and Morgan, W.F.  Apoptosis, reproductive integrity, and oxidative stress in Chinese hamster ovary cells with compromised genomic integrity.  Cancer Res. 58, 3712-3718, (1998).

Hollander, M.C., Sheikh, M.S., Bulavin, D., Lundgren, K., Augeri-Henmueller, L., Shehee, R., Molinaro, T., Kim, K., Tolosa, E., Ashwell, J.D., Rosenberg, M.D., Zhan, Q., Gernandez-Salguero, P.M., Morgan, W.F., Deng, C-X. and Fornace, A.J.  Genomic instability in gadd45 –deficient mice.  Nature Genetics, 23, 176-184, (1999).

Limoli, C.L., Giedzinski, E., Morgan, W.F. and Cleaver, J.E.  Polymerase n deficiency in the XP variant uncovers an overlap between the S phase checkpoint and double-strand break repair.  Proc. Natl. Acad. Sci. (USA) 97, 7939-7946 (2000).

Limoli, C.L., Ponnaiya, B., Corcorin, J.J., Lyons, A., Giedzinski, E., Kaplan, M.I., Hartmann, A. and Morgan, W.F.  Genomic instability induced by high and low LET ionizing radiation.  Advances in Space Research 25:2107-2117, (2000).

Limoli, C.L., Kaplan, M.I., Giedzinski, E. and Morgan, W.F.  Attenuation of radiation-induced genomic instability by free radical scavengers and cellular proliferation. Free Radical Biology & Medicine, 31: 10-19 (2001).

Williams B.R., Mirzoeva, O.K., Morgan, W.F., Lin, J., Dunnick, W. and Petrini, J.H.J.  A murine model of Nijmegen breakage syndrome.  Current Biol. 12: 1-6 (2002).

Paris, F., Perez, G.I., Haimovitz-Friedman, A., Nguyen, H., Fuks, Z., Bose, M., Ilagan, A., Hunt, P.A., Morgan, W.F., Tilly, J.L. and Kolesnick, R.  Sphingosine 1-phosphate preserves fertility in irradiated female mice without propagating genomic damage in offspring.  Nature Med. 8, 901-902, (2002).

Nagar, S., Smith, L.E. and Morgan, W.F.  Characterization of a novel epigenetic effect of ionizing radiation: the death inducing effect.  Cancer Res. 63, 324-328, (2003).

Morgan, W.F., Non-targeted and delayed effects of exposure to ionizing radiation: I.  Radiation induced genomic instability and bystander effects in vitro.  Radiat. Res. 159, 567-580 (2003).

Morgan, W.F., Non-targeted and delayed effects of exposure to ionizing radiation: II.  Radiation induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects.  Radiat. Res. 159, 581-596 (2003).

Limoli, C.L., Giedzinski, E., Morgan, W.F., Swarts, S.G., Jones, G.D.D. and Hyun, W.  Persistent oxidative stress in chromosomally unstable cells.  Cancer Res. 63, 3107-3111 (2003).

Huang, L., Grim, S., Smith, L.E., Kim, P.M., Nickoloff, J.A., Goloubeva, O.G. and Morgan, W.F.  Ionizing radiation induces delayed hyperrecombination in mammalian cells.  Mol. Cell Biol. 24, 5060-5068 (2004).

Snyder, A.R. and Morgan, W.F., Lack of consensus gene expression changes associated with radiation-induced chromosomal instability.  DNA Repair 4, 958-970 (2005).

Durant, S.T., Paffett, K.S., Shrivastav, M., Timmins, G.S., Morgan, W.F. and Nickoloff, J.A.  UV radiation induces delayed hyperrecombination associated with hypermutation in human cells.  Mol. Cell Biol. 26, 6047-6055 (2006)

Kim, G.J., Fiskum, G. and Morgan, W.F.  A role for mitochondrial dysfunction in perpetuating radiation induced genomic instability.  Cancer Res. 66, 10377-10383 (2006).

Huang, L., Nickoloff, J.A., Kim, P.M. and Morgan, W.F.  Targeted and non-targeted effects of low-dose ionizing radiation on delayed genomic instability in human cells.  Cancer Res. 67, 1099-1104 (2007).

Morales, M., Liu, Y., Laiakis, E.C., Morgan, W.F., Nimer, S.D., and Petrini, J.H.J., DNA damage signaling in hematopoietic cells:  A role for Mre11 complex repair of topoisomerase lesions.  Cancer Res., 68, 2186-2193 (2008).

Dziegielewsi, J., Baulch, J.E., Goetz, W., Coleman, M.C., Spitz, D.R., Murley, J.S., Grdina, D.J. and Morgan, W.F.: WR-1065, the active metabolite of amifostine, mitigates radiation induced delayed genomic instability.  Free Radical Biol. & Med. In press

NASA Announces 2009 Space Radiation Summer School

NASA’s Space Radiation Program has announced that applications may be submitted for its annual Space Radiation Summer School (“NSRSS”) at the U.S. Department of Energy's Brookhaven National Laboratory.  The Summer School offers graduate students and postdoctoral students the opportunity to learn about the unique characteristics of space radiation and how to perform experiments exposing targets to high energy, high charge (HZE) particles. NSRSS was designed to provide a “pipeline” of researchers to tackle the challenges of harmful radiation exposure to humans who will travel on space exploration missions. Co-sponsored by NASA’s Space Radiation Research Program, Brookhaven National Laboratory, U.S. Department of Energy, Pacific Northwest National Laboratory, Loma Linda University Medical Center, and the Universities Space Research Association; the three-week course was piloted in 2004 as an invitational program.  Following the success of the first summer school, the course has been offered since then  through an open and increasingly competitive application process with applicant eligibility opened to both U.S. Citizens and foreign nationals.  Interest in the NSRSS is truly global with applications received from more than 20 countries over the last four years.

The course is taught by leading university and national laboratory biologists and physicists actively engaged in NASA space radiation research and BNL experts in heavy ion experimentation and methods. Each “professor” lectures on his/her research specialty: DNA damage and repair, genotoxicity measurements, cell cycle checkpoints and apoptosis, the bystander effect, genomic instability, neurodegeneration, tissue remodeling, and the relationships of these processes to carcinogenesis and late degenerative effects following exposure to space radiation, as well as the space radiation environment, physics and biochemistry of charged particle interaction with condensed matter, ionizing radiation dosimetry, and accelerator operations.

The 2009 course Scientific Director is William F. Morgan, Ph.D., D. Sc. Dr. Morgan is the Director of Radiation Biology and Biophysics in the Biological Sciences Division of the Pacific Northwest National Laboratory (PNNL), Richland, Washington.

Eligibility requirements and a link to the Workshop application form may be found at this link: http://www.dsls.usra.edu/spacerad/2009/application.html

The deadline for application to the 2009 program is 11:59 PM, Saturday, February 28, 2009.

20th Annual NASA Space Radiation Annual Investigators’ Workshop and Heavy Ions in Therapy and Space Symposium

Heavy Ion Symposium 2009 PosterDLR, the German Aerospace Center, has announced topics for the 20th Annual NASA Space Radiation Annual Investigators’ Workshop and Heavy Ions in Therapy and Space Symposium , scheduled for July 6–10, 2009 in Cologne, Germany. 

The topics to be covered during the Symposium in both plenary and poster sessions include:

  • Cell and tissue radiobiology
  • DNA damage and repair
  • Signaling and pathways in cell biology
  • Late effects of heavy ions
  • Individual radiosensitivity
  • Bystander/abscopal effects
  • Heavy ion carcinogenesis
  • CNS damage
  • Countermeasures
  • Dosimetry in space
  • Treatment planning
  • Medical physics
  • Clinical results – studies and status reports on treatment
  • Beam production and dose delivery methods
  • Quality assurance and robotics

Some travel funding will be available for students, and there will be a student poster contest.  For additional details, please visit the Student Travel Awards section of the website.

The Symposium, also sponsored by GSI, NASA, ESA, and IHK Köln, includes the 5th International Workshop on Space Radiation Research (IWSRR), the 12th Workshop on Ion Beam in Biology and Medicine (IBIBAM), the 20th Annual NASA Space Radiation Investigators’ Workshop, and the 1st ESA Space Radiation Investigators’ Meeting (ESARAD).

Following the Heavy Ions in Space Symposium, the 9th International Symposium on Chromosomal Aberrations (ISCA) will be held in St. Goar, Germany.  The ISCA, from July 11–12, 2009, is limited to 80 participants on a first come, first served basis.  Abstracts are due on March 15, 2009 and will be divided into oral and poster sessions.

The major topics of ISCA will be the following:

  • Chromosome structure and function
  • Mechanisms of chromosome aberration formation
  • New techniques for detection
  • Cytogenetic epidemiology
  • Biodosimetry
  • Chromosomal instability
  • Clinical cytogenetics
  • Hereditary effects
  • Cytogenetic effects of heavy ions
  • Cytogenetic effects of non-ionizing radiation

Registration information may be found at both sites.

Robert Katz Publications Now Online

Dr. Robert KatzThe University of Nebraska Lincoln has published, on Digital Commons, downloadable publications by Professor Robert Katz. Dates of the publications range from 1943 to 2003. Many of the recent publications originated from his collaborations with NASA space radiation investigators.

The URL for the publications is the following: http://digitalcommons.unl.edu/physicskatz/

Robert Katz originated the track-structure theory and its application to heavy ion radiobiology. Professor Katz noted the following: ”Track models have been built by calculating the effect of individual delta rays on the irradiated detectors. Such models, often made by Monte Carlo methods have not yielded successful models of heavy ion tacks. Our work (Katz and students J.J. Butts and E.J. Kobetich) has focused on the radial distribution of dose from delta rays about the ion's path, coordinating this with knowledge of damage by x-rays at the same dose. Radial integration of this damage yields the damage cross-section, similar in principle to the concept that cross-section is the probability of damage per unit fluence. This procedure has been successful, when first applied to radiobiological data from the inactivation of dry enzymes and viruses by energetic heavy ions, and many later phenomena. Following the radiobiological concept of target theory we speak of the ”hittedness“ of a detector. There are many 1-hit detectors, but less sensitive detectors can be 2- hit or more, implying the number of electron transits through the sensitive target of the detector.“

”A more complex radiobiological system consists of sets of biological cells irradiated consecutively with different beams of heavy ions. Here the survival curves take on different shapes. Our model has been extended to note that the biological effect may be produced by collision with the ion nucleus, which we term ion-kill, and interaction with the delta rays, termed gamma-kill whose response follows the response to gamma rays.“

”This model requires a single set of 4 parameters to fit the entire set of data. Further, this model accommodates a mixed radiation field, composed of the ion beam and a supplementary c-ray exposure whose dose is added to the gamma kill dose.“

Readers interested in particle tracks and the work of Professor Katz and his laboratory will find these articles useful to their understanding of the theory.

Facebook Group Established for NASA Space Radiation Summer School Alumni

A group has been has been established on the Facebook social networking site http://www.facebook.com to facilitate interaction among alumni of the NASA Space Radiation Summer Schools from 2004 through 2008. Alumni are invited to join the group to catch up with the members of their classes, to follow their careers, and to discuss items of common interest.

Because this is a closed Facebook group, potential members must be invited to join. To secure an invitation, please search for ”NASA Space Radiation Summer School“ and click on ”Request to join.“