Life Sciences Division Newsletter
In this issue:
Scientific News »
- Un-Junking Junk DNA »
- New Imaging Technique Identified to Monitor Progression of Heart Failure »
- The Inner Workings of a Bacterial Black Box Caught on Time-Lapse Video »
- Mina Bissell Comments on The Risks of the Replication Drive »
- Recent Publications »
- Lab Director Alivisatos Calls Out Work by Costes and Tang at All-Hands Meeting »
- Biosciences Expert Advisory Committee Meets on November 7 »
- Honoring Those Who Served: Lab Vets, Including Tony Smith, Share Their Stories »
- Helen Budworth Mentors Emerging Leader from Nigeria in TechWomen Program »
- Berkeley Lab Team Completes Dirty Girl Mud Run Raising Women’s Health Awareness »
- New Hires and Departures: Welcomes and Goodbyes »
A recent study shines a new light on molecular tools our cells use to govern regulated gene expression. Researchers uncovered a novel mechanism that allows proteins that direct pre-mRNA splicing – RNA-binding proteins – to induce a regulatory effect from greater distances than was thought possible. The discovery expands potential targets of rationally designed therapies which could correct molecular defects through antisense RNA oligonucleotides – small pieces of DNA or RNA that can bind to specific RNA targets to either block interactions with RNA-binding proteins and/or initiate degradation of the target RNA. Study co-authors include Sherry Gee, Marilyn Parra, Dana Ghanem, and Henry Marr of the Life Sciences Division.
The study was in collaboration with researchers at the University of California, San Diego School of Medicine. It was published online in advance of print November 10 in the journal Nature Structural and Molecular Biology. Co-lead investigator on the study is Life Sciences John Conboy. More »
Adapted from Today at Berkeley Lab, November 15, 2013
Anatomy of a normal and hypertrophied heart
In a recent publication of Journal of Nuclear Medicine, a team of scientists from Berkeley Lab, the University of Utah, and UC San Francisco describe a new imaging technique used to monitor the progression of heart failure. Led by Life Sciences Grant Gullberg, the team used microPET/CT imaging (a molecular level functional imaging modality) to periodically track changes in metabolism and blood flow for controls and spontaneously hypertensive rats (SHR) that developed left ventricular hypertrophy with age and eventually heart failure. These imaging techniques could be translated directly to humans to help improve diagnosis, risk stratification and therapy management for patients with heart failure.
Left ventricular hypertrophy is the enlargement, thickening and stiffening of the muscle (myocardium) that makes up the wall of the main pumping chamber of the heart. Hypertrophy can develop in response to hypertension, characterized by high blood pressure that requires the left ventricle to work harder. Ultimately it can lead to heart failure, when the heart no longer provides enough blood to meet the metabolic needs of the body.
Under healthy conditions, fatty acids are the preferred metabolic fuel and account for 60-70% of energy production. Fatty acids provide more than twice as much energy per mass than glucose. As hypertrophy develops, the heart exhibits impaired metabolism, contractile dysfunction and left ventricular remodeling. In this diseased state, it’s believed that the heart switches to rely on glucose as the major fuel.
MicroPET/CT scanner at UCSF China Basin that was used for the imaging studies (Photo provided by Youngho Seo from UCSF)
Using microPET/CT, the research team tracked changes in glucose metabolism, fatty acid metabolism and perfusion as a function of hypertrophy and age in the same control and SHR rats over a two-year period under fasting conditions. They imaged with the long-chain fatty-acid analog [18F]Fluoro-6-heptadecanoic acid (FTHA) and glucose analog [18F]Fluorodeoxyglucose (FDG) PET radiotracers to track metabolic changes. The radiotracer [18F]Fluorodihydrototenol (FDHROL), an analog of the mitochondrial binding agent rotenone, was also used to evaluate perfusion in the heart. The ejection fraction, a measure of the percentage of blood leaving the heart each time it contracts, was quantified. Blood samples were also obtained and analyzed for circulating glucose, insulin and free fatty acid concentrations.
The authors found that metabolic changes preceded mechanical alterations in the onset of left ventricular hypertrophy. Myocardial FDG uptake (glucose metabolism) and FTHA uptake (fatty acid metabolism) were both higher for SHR than controls even at eight months of age, before significant hypertrophy was evident from the ejection fraction. In addition, FDHROL demonstrated outstanding flow versus extraction characteristics, proving it to be an outstanding PET radiotracer for analyzing perfusion. Thus, PET/CT imaging with these novel radiotracers could be translated to the clinic for early stage identification and therapy management of patients with cardiac hypertrophy.
Hernandez AM, Huber JS, Murphy ST, Janabi M, Zeng GL, Brennan KM, O’Neil JP, Seo Y, Gullberg GT. Longitudinal evaluation of left ventricular substrate metabolism, perfusion and dysfunction in the SHR model of hypertrophy using microPET/CT imaging. Journal of Nuclear Medicine. 54(11), November 2013. Article »
[By Jennifer Huber]
Cyanobacteria, found in just about every ecosystem on Earth, are one of the few bacteria that can create their own energy through photosynthesis and “fix” carbon – from carbon dioxide molecules – and convert it into fuel inside of miniscule compartments called carboxysomes. Using a pioneering visualization method, researchers from UC Berkeley and the Joint Genome Institute made what are, in effect, movies of this complex and vital cellular machinery being assembled inside living cells. They observed that bacteria build these internal compartments in a way never seen in plant, animal and other eukaryotic cells: from the inside out. More »
All time-lapse fluorescence microscopic imaging was conducted at the Life Sciences Advanced Microscopy Facility with assistance of Facility Manager Michelle Scott.
Adapted from Today at Berkeley Lab, November 27, 2013
The push to replicate research findings could shelve promising lines of inquiry and unfairly damage the reputations of careful, meticulous scientists, says Mina Bissell, distinguished scientist in the Life Sciences Division. Writing a commentary in the journal Nature, Bissell, a renowned breast cancer researcher, expressed concern about a drive underway by NIH and others in the biological fields to have results replicated by an independent, self-appointed entity that will charge for the service. Although reproducibility is the bedrock of the scientific process, Bissell notes that those who try to repeat research often lack the time, funding, resources and expertise to do so. “It is sometimes much easier not to replicate than to replicate studies, because the techniques and reagents are sophisticated, time-consuming and difficult to master,” she says.
Adapted from Today at Berkeley Lab, November 26, 2013
What follows is a review of Life Sciences recent publications.
Becker-Weimann S, Xiong G, Furuta S, Han J, Kuhn I, Akavia UD, Pe'er D, Bissell MJ, Xu R. NFkB disrupts tissue polarity in 3D by preventing integration of microenvironmental signals. Oncotarget. 2013 Oct 14. [Epub ahead of print] PMID: 24243820 Abstract »
Blakely EA, Blakely WF, Scott BR. Howard s. Ducoff, Ph.D. 1923-2012. Radiation Research. 2013 Nov;180(5):556-7. PMID: 24245659
Daemen A, Griffith OL, Heiser LM, Wang NJ, Enache OM, Sanborn Z, Pepin F, Durinck S, Korkola JE, Griffith M, Hur JS, Huh N, Chung J, Cope L, Fackler MJ, Umbricht C, Sukumar S, Seth P, Sukhatme VP, Jakkula LR, Lu Y, Mills GB, Cho RJ, Collisson EA, Van't Veer LJ, Spellman PT, Gray JW. Modeling precision treatment of breast cancer. Genome Biology. 2013 Oct 31;14(10):R110. [Epub ahead of print] PMID: 24176112 Abstract »
Dyer KN, Hammel M, Rambo RP, Tsutakawa SE, Rodic I, Classen S, Tainer JA, Hura GL. High-throughput SAXS for the characterization of biomolecules in solution: a practical approach. Methods Molecular Biology. 2014;1091:245-58. PMID: 24203338 Abstract »
Hernandez AM, Huber JS, Murphy ST, Janabi M, Zeng GL, Brennan KM, O’Neil JP, Seo Y, Gullberg GT. Longitudinal evaluation of left ventricular substrate metabolism, perfusion and dysfunction in the SHR model of hypertrophy using microPET/CT imaging. Journal of Nuclear Medicine. 2013 Nov;54(11):1938-45.. Epub 2013 Oct 3. PMID: 24092939 Abstract »
Howes SC, Alushin GM, Shida T, Nachury MV, Nogales E. Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure. Molecular Biology Cell. 2013 Nov 13. [Epub ahead of print] PMID: 24227885 Abstract »
Hung MS, Xu Z, Chen Y, Smith E, Mao JH, Hsieh D, Lin YC, Yang CT, Jablons DM, You L. Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model. International Journal of Oncology. 2013 Nov;43(5):1517-22. Epub 2013 Sep 4. PMID: 24008396 Abstract »
Jones T, Budinger T. The potential for low dose functional studies in maternal-fetal medicine using combined PET and MRI. Journal of Nuclear Medicine. 54(11):2016–2017, November 1, 2013 [Letter to the Editor]. Article »
Lee SE, Alivisatos AP, Bissell MJ. Toward plasmonics-enabled spatiotemporal activity patterns in three-dimensional culture models. Systems Biomedicen. 2013 Jan;1(1). PMID: 24224142 Abstract »
Lovci MT, Ghanem D, Marr H, Arnold J, Gee S, Parra M, Liang TY, Stark TJ, Gehman LT, Hoon S, Massirer KB, Pratt GA, Black DL, Gray JW, Conboy JG, Yeo GW. Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges. Nature Structural Molecular Biology. 2013 Nov 10. [Epub ahead of print] PMID: 24213538 Abstract »
Nan X, Collisson EA, Lewis S, Huang J, Tamgüney TM, Liphardt JT, McCormick F, Gray JW, Chu S. Single-molecule superresolution imaging allows quantitative analysis of RAF multimer formation and signaling. Proceedings of the National Academy of Science U.S. A. 2013 Nov 12;110(46):18519-24. Epub 2013 Oct 24. PMID: 24158481 Abstract »
Oh H, Jagust WJ. Frontotemporal network connectivity during memory encoding is increased with aging and disrupted by beta-amyloid. Journal of Neuroscience. 2013 Nov 20;33(47):18425-37. PMID: 24259567 Abstract »
Overhoff MG, Garbe JC, Koh J, Stampfer MR, Beach DH, Bishop CL. Cellular senescence mediated by p16INK4A-coupled miRNA pathways. Nucleic Acids Research. 2013 Nov 11. [Epub ahead of print] PMID: 24217920 Abstract »
Petzold CJ, Schwarz RI. Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid. PeerJ. 2013 Oct 29;1:e192. PMID: 24244914 Abstract »
Stamper EL, Rodenbusch SE, Rosu S, Ahringer J, Villeneuve AM, Dernburg AF. Correction: Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint. PLoS Genetics. 2013 Sep;9(9). Epub 2013 Sep 23. PMID: 24204328 Article »
Wallner PE, Anscher MS, Barker CA, Bassetti M, Bristow RG, Cha YI, Dicker AP, Formenti SC, Graves EE, Hahn SM, Hei TK, Kimmelman AC, Kirsch DG, Kozak KR, Lawrence TS, Marples B, McBride WH, Mikkelsen RB, Park CC, Weidhaas JB, Zietman AL, Steinberg M. Current status and recommendations for the future of research, teaching, and testing in the biological sciences of radiation oncology: report of the American Society for Radiation Oncology Cancer Biology/Radiation Biology Task Force, Executive Summary. International Journal of Radiation Oncology Biological Physiology. 2013 Nov 14. pii: S0360-3016(13)03180-5. [Epub ahead of print] PMID: 24246724 Abstract »
Wirth M, Villeneuve S, Haase CM, Madison CM, Oh H, Landau SM, Rabinovici GD, Jagust WJ. Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people. JAMA Neurology. 2013 Oct 28. [Epub ahead of print] PMID: 24166579 Abstract »Zhao W, Saro D, Hammel M, Kwon Y, Xu Y, Rambo RP, Williams GJ, Chi P, Lu L, Pezza RJ, Camerini-Otero RD, Tainer JA, Wang HW, Sung P. Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing. Nucleic Acids Research. 2013 Oct 22. [Epub ahead of print] PMID: 24150939 Abstract »
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Lab Director Paul Alivisatos gave a "State of the Lab" talk in the Building 50 Auditorium on November 7 to share his thoughts about Berkeley Lab's strategy, after which he took questions from the audience. For those who were not able to attend the all-hands meeting in person, the meeting was streamed live; an event moderator collected questions emailed.
In his presentation, Alivisatos made several references to the Life Sciences Division. Talking about the research area of human health impacts of radiation exposure he said that “The Life Sciences group continues to do really remarkable work in this area.” He referenced a paper (by Sylvain Costes and Jonathan Tang) that came out recently showing the molecular mechanism by which radiation exposure of young women raises their risk of breast cancer. He also remarked “how well they [Life Sciences] are integrating their life sciences research related to health with the energy and environment goals of the Laboratory--It is a great development.” You can watch the Director’s presentation here.
On November 7 the Biosciences Executive Committee – consisting of Biosciences Area leaders - met with the Biosciences Expert Advisory Committee (BEAC) at Berkeley Lab for the first time after the Biosciences Strategic Plan (BSP) was released earlier this year. Objectives of the meeting included presenting the details of the 10 year scientific BSP, and sharing some of the Area’s implementation progress toward its four goals: Energy Research Focus (mentor: Edward Rubin), Environment Research Focus (mentor: Susan Hubbard), Health Research Focus (mentor: Gary Karpen), and Biomanufacturing Research Focus (mentor: Adam Arkin). These morning progress presentations were designed to cover, for each four goals, details of the BSP in 15 minutes or less with the goal’s mentor first presenting BSP specifics and setting the context for two implementation talks that followed.
Most implementation talks were the "grand challenge" type, where the ideas have been developed, but others were of the variety where proposals have already been submitted under the strategy. Life Sciences presenters included Health Research Focus mentor Gary Karpen, Mandana Veiseh who presented on “High-Performance Biosensors,” and Sylvain Costes who presented on “Human Biomarker Landscape in Response to Environmental Challenges.” Other implementation talk presenters included Nathan Hillson (PBD), Janet Jansson (ESD), Peter Nico (ESD), Sarah Richardson (PBD), Steven Singer (ESD), and Chia-Lin Wei (GD).
Talks were preceded by an introduction to Biosciences by Jay Keasling, and an overview of the BSP by Mary Maxon. The afternoon agenda included a BEAC Executive session, an outbrief and an Industry Advisory Board Discussion lead by Keasling. Discussions were continued in the evening at a working dinner that concluded the meeting. Attending BEAC members included Frances Arnold (remotely), Janet Braam, Charles Craik, Edward DeLong, Edward Penhoet, John Pierce, Martha Schlicher, Kate Scow, James Tiedje. The Biosciences Area website, including the BSP and a complete list of the BEAC members, can be found here.
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Every year on November 11, Veterans Day, our nation honors those who have protected our country through service in the armed forces. At Berkeley Lab, there are 101 veterans out of a total of 8,086 employees and affiliates, according to Human Resources. On this day, three Berkeley Lab vets — Terry Hamilton, Life Sciences Tony Smith, and Diana Attia — share their stories. More »
Adapted from Today at Berkeley Lab, November 11, 2013
Along with four Berkeley Lab colleagues, life scientist Helen Budworth of the McMurray lab in November completed her participation in the TechWomen program 2013, an initiative of the U.S. Department of State's Bureau of Educational and Cultural Affairs. TechWomen, according to the program’s website “empowers, connects, and supports the next generation of women leaders in science, technology, engineering, and mathematics (STEM) from Africa and the Middle East by providing them the access and opportunity needed to advance their careers, pursue their dreams, and inspire women and girls in their communities.” Also, “Through mentorship and exchange, TechWomen strengthens participants’ professional capacity, increases mutual understanding between key networks of professionals, and expands girls’ interest in STEM careers by exposing them to female role models.” Time for a few questions for Budworth about her volunteering in this program:
- How did you learn about the TechWomen program?
“I heard about the program through the Berkeley Lab’s Women Scientists and Engineers Council (WSEC), which I am a member of.”
- Who was the Emerging Leader you worked with?
“I was mentoring Dr. Angela Makolo, a computational biologist from the University of Ibadan in Nigeria. She is a lecturer in the university’s Department of Computer Science and heads a bioinformatics research group there.” Makolo, while here, was co-hosted by a cultural mentor Patience Fielding, who works in the area of international education at UC Berkeley, Budworth adds.
Angela Makalo visits NERSC
- TechWomen’s Emerging Leaders and Mentors work on “mutually beneficial projects”; what did you work on?
“Dr. Makolo and I worked on a project to identify unique sequence motifs and chromatin marks at fragile sites in the human genome. Dr. Makolo’s background is in computational techniques for motif identification and extraction. Her work has characterized the malaria parasite transcription factors and their DNA binding sites. The project utilized this experience for applications looking at unstable chromosome regions that are associated with human genetic disease.”
- How long did you work together?
“Dr. Makolo and I communicated regarding the project in September prior to her arrival in the U.S. She was hosted at LBNL only for the month of October. We are hoping to continue the collaboration and have continued to communicate since she has returned to her home institution.”
- Would you recommend the program to others?
“Yes, I would recommend the TechWomen program; it was a very worthwhile experience. The program connects you with other women in science working in the Bay Area, and it also connects you with women in science across the world. The value of that diverse, international perspective is huge.”
To learn more about the 2013 Emerging Leaders, including Makolo, visit the Techwomen website here. Also, Makolo, who calls the program “a dream come true,” wrote a guest blog post entitled “Emerging Leaders Go Beyond the Mentorship” which is posted on that website.
More about TechWomen 2013 and Berkeley Lab’s participation can be read in NERSC’s article “Lab Hosts Five Emerging Leaders During TechWomen 2013”:
[Today at Berkeley Lab] For Aseel Honein, an architect, teacher and design activist from Lebanon, spending a month collaborating with scientists at Berkeley Lab was a dream come true. She got the opportunity to do so through the TechWomen 2013 program, which brought 76 women from 16 Middle Eastern and African countries to the U.S. in October for a five-week professional mentoring program. Five of these emerging leaders were hosted by colleagues from the Lab who worked closely with them on projects related to their burgeoning careers. More »
A Berkeley Lab women team successfully completed the Dirty Girl Mud Run in Pleasanton on October 26, raising breast and ovarian health awareness along the way. The team, who calls themselves the “Walkie Talkies,” includes Life Sciences Davina Abram, Karen Dickinson-Mazzei, Kristine Gee, Helen Jefferson, Yolanda Reyna, and Kristi Shaw; as well as Janice Mann, Sonia Dominguez; and Kathryn Hoffman of CHORI.
Walkie-Talkies team members (l-r): Abram, Dominguez, Mann, Gee, Jefferson, Reyna, Shaw, Hoffman, and Dickinson-Mazzei
Dirty Girl is a 5K women-only run for women of all ages and athletic abilities. It is not a "race" in the traditional sense; it is an untimed obstacle course designed to push participants slightly out of their comfort zone, but only as far as they are comfortable going. “Dirty Girl is a for-profit company that believes strongly in the cause of finding a cure for breast cancer, in educating women about health and in supporting cancer victims and survivors. The company will be contributing $250,000 to Bright Pink in 2013 to further this mission,” their website reads. With the joint goal of empowering women to lead healthy lifestyles, Dirty Girl and Bright Pink - their official charity partner - urge the hundreds of thousands of women who participate annually in Dirty Girl events to be proactive with their breast and ovarian health.
Asked about the team’s name Helen Jefferson said, “We have often walked around the Potter area and thought this would be a fun event to do as a group.” It was the first year for the team to participate but not the last, Jefferson adds. “Some have signed up for another run in San Francisco in March and most of us have committed to participate September 2014 in Pleasanton.” If interested in joining the team for any of the upcoming Dirty Girl events contact team leader Kristi Shaw or stop by and see one of the team members in room 143 at 717 Potter Street.
Eduardo Jose Pena, visiting researcher, Downing lab, per November 15
Ryan John Hartnett, student assistant, Bizarri lab, per November 8
Elaine Wang, research assistant, Costes lab, per November 1
Karen Omoto, senior proposal specialist, proposals group, per mid-December
Omoto has been offered and has accepted a new role with Berkeley Lab’s Office of Sponsored Projects and Industry Partnerships which allows her to broaden her skill set and career advancements. She has been a very strong contributor to the Life Sciences proposals group and to the finance team generally and she will be very greatly missed.
Erin Reiche, principal proposal specialist, proposals group
Following a medical leave of absence, Reiche has retired from Berkeley Lab. She joined Life Sciences in 2005 and provided outstanding proposal support for more than seven years.
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