A team of 95 physicists, engineers, mathematicians, chemists, computational scientists and biologists working on different experiments in 20 US laboratories has gained a new perspective on cancer by pooling their research in a coordinated way. The motivation was to gain insights into the differences between non-malignant and metastatic cancer cells – those that leave the primary tumor and spread to other organs.

Although most aspects of the study have been conducted before, attempts to integrate the results have been hampered by the diversity of samples used. For the first time, a wide range of experiments was conducted simultaneously on the same standardized cells. The results were just published in Nature’s Scientific Reports paper entitled, A physical sciences network characterization of non-tumorigenic and metastatic cells (10.1038/srep01449).

Using two breast cell lines, in which cells are artificially immortalized and bred in laboratories, the scientists focused on the physical changes that accompany the transition of cancer cells to a motile, metastatic form. While metastasis is generally recognized as a critical step in the progression of cancer, there is an incomplete understanding of the physical biology of this transformation. The researchers state that: “Understanding the physical forces that metastatic cells experience and overcome in their microenvironment may improve our ability to target this key step in tumor progression.”

The research was conducted by the network of 12 Physical Sciences-Oncology Centers around the country (PS-OCs), under the auspices of the Office of Physical Sciences-Oncology at the National Cancer Institute. The centers were set up 3 years ago to foster collaboration between physical scientists, biologists and oncologists in order to achieve new insights into cancer.

Laboratories in each center were supplied with identical cell lines and common reagents, and considerable effort was expended to ensure that all the conditions were standardized and documented at regular intervals. This allowed the laboratories to leverage their own expertise and for the results of all the measurements to be integrated across the study.

The number of distinct techniques used to characterize the cells was impressive — more than would be possible in any of the individual labs on their own. One of the lead authors of the paper, Jack (Rory) Staunton, a PhD physics student at Arizona Statue University, comments:

“The work has enabled a comprehensive cataloging and comparison of the physical characteristics of non-malignant and metastatic cells, and the molecular signatures associated with those characteristics. This made it possible to identify unique relationships between observations.”

“We compared the stiffness of normal breast cells and highly metastatic breast cancer cells, and found the cancer cells to be significantly more ‘squishy’ or deformable,” Staunton said. “This makes sense because in order for a cell to metastasize, it has to squeeze through tight passages in the lymphatics and microvasculature, so being squishy helps cancer cells spread through the body.”

Other techniques used included atomic force microscopy, ballistic intracellular nano-rheology, cell surface receptor expression levels, differential interference contrast microscopy, micro-patterning and extracellular matrix secretion, and traction force microscopy.

Staunton, who has been involved in ASU’s PS-OC center since its inception three years ago says the experience has helped his growth as a researcher: “It is the perfect habitat for budding scientists and for trans-disciplinary collaborations.”

Although the cell line exercise involved considerable organization and commitment, it sets a benchmark for future interdisciplinary work in cancer research, and is expected to become the model for future large collaborations.

AS THE US faces up to its “fiscal cliff” of massive spending cuts, a major issue is burgeoning health costs. High on the list of those costs is cancer therapy, with the clamour for hugely expensive drugs – many of which have little or no clinical benefit – set to grow as baby boomers age.

Cancer research swallows billions of dollars a year, but the life expectancy for someone diagnosed with cancer that has spread to other parts of the body has changed little over several decades. Therapy is often a haphazard rearguard action against the inevitable. And the search for a general cure remains as elusive as ever.

Recognising this depressing impasse, the US National Cancer Institute (NCI) took a bold step in 2008 by deciding that the field might benefit from the input of mathematicians and physical scientists, whose methods and insights differ markedly from those of cancer …

Symposium Program
Speaker Biographies

Cancer and the Desert – A Crossroads between Astrobiology and Cancer Research

Gareth Owen

Gareth Owen

Paul Davies and Pedro Zamorano

Question from John Coates

Felipe Court

Paul Davies and Pedro Zamorano

Paul Davies

Pauline Davies

Pauline Davies

Speaker: Stuart Lindsay, PhD, specializes in biophysics at the molecular level and scanning probe microscopy. Much of his work is aimed at speedier diagnosis and an understanding of the molecular basis of disease. He holds 29 US patents and is a technology advisor for the Atomic Force Microscope Division of Agilent Technologies. Agilent has acquired Molecular Imaging Corporation, which he co-founded in 1993.

Location: Biodesign Auditorium

Web Cast: View Web Cast Video

Date & Time: September 20th, 2012 12:00 p.m.

Title: Epigenetics – Physics or Magic?

Abstract: To a physicist, epigenetics – the passing of heritable traits to daughter cells without alteration of the genome – seems like magic. Yet it surely lies at the heart of cancer, as cancerous phenotypes can be switched on and off without alteration of the genome. Together with the Henikoff lab at Fred Hutchinson Cancer Research Center, we have been looking for physical manifestations of epigenetic coding. We started by looking at modifications and variants of histones, but these seem to be unlikely candidates for heritable markers. Instead, it appears that transcription factors (which are passed on at cell division) are the controlling factor. We have also studied methylation of DNA, a modification that imparts permanent silencing. Nucleosomes reconstituted on methylated DNA are intrinsically harder to open, implying a mechanical change in the DNA on methylation. Light scattering studies(by Sara Vaiana and Stephanie Cope) shows that methylation makes no difference in bulk solution. In contrast, AFM studies show that DNA shortens and stiffens with methylation at a solid-liquid interface. We therefore conclude that the hydrophobic interaction plays a role in keeping methylated DNA in place on nucleosomes.

Thank you and if you have questions please contact Amanda Wilber! And don’t forget, coffee will be served!

Amanda Wilber, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

480.965.3860 | Fax: 480.965.6362
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The National Cancer Institute’s annual PS-OC network conference will convene at the Scottsdale Plaza Resort, April 16-19. Several hundred participants are expected. The meeting will begin with a Young Investigators Forum, and will include cutting edge research reports from the twelve Centers in the network.

Speaker: Steve Henikoff, PhD, received a BS degree in Chemistry from the University of Chicago and a Ph.D. degree in Biochemistry and Molecular Biology from Harvard University, and carried out postdoctoral research at the University of Washington. He joined the Fred Hutchinson Cancer Research Center in Seattle in 1981, where he is a Member of the Basic Sciences Division and an Affiliate Professor of Genome Science at the University of Washington. He has been an Investigator of the Howard Hughes Medical Institute since 1990 and a Member of the US National Academy of Sciences since 2005. He is co-Editor-in-Chief of Epigenetics & Chromatin, a member of the Editorial Boards of Trends in Genetics, Current Opinion in Genetics and Development and Genome Biology, and a member of the Scientific Adisory Boards of Epizyme, Inc. and the Chicago Biomedical Consortium. His laboratory studies chromatin processes, epigenetic inheritance, centromere structure, function and evolution, and develops tools for epigenomics.

Location: Biodesign Auditorium

Web Cast: View Web Cast Video

Date & Time: September 6th, 2012 12:00 p.m.

Title: Histone variants, nucleosome dynamics and epigenetics

Abstract: Dr. Henikoff will talk about histone variants, nucleosome dynamics and epigenetics.

Thank you and if you have questions please contact Amanda Wilber! And don’t forget, coffee will be served!

Amanda Wilber, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

480.965.3860 | Fax: 480.965.6362
email hidden; JavaScript is required

About:
The Arizona State University Physical Sciences‐Oncology Center (PS‐OC) is one of 12 PS‐OCs funded by the National Cancer Institute. Funding is available to support a pilot project that revolves around the intersection of cancer biology and the physical sciences. The due date is August 31, 2012.
Qualifications and Requirements:
The lead applicant must be ASU‐affiliated although team members from outside are welcome. The proposed work must focus on an innovative idea or previously untested hypothesis. Proposals from current PS‐OC members must represent new work and not enhancements of existing PS‐OC aims. The total funds available are $25,000 for six months. Depending on availability of funds, an additional $25,000 for a total duration of twelve months may be available. The funds should be spent primarily on supplies and trainee salaries. No faculty salaries will be supported.
Application Requirements:
Applications should include the following elements:
1. Background, including preliminary work (1⁄2 page max)
2. Specific aims including duration of each (1⁄2 page max)
3. Experimental/theoretical design (1 page max)
4. Budget using NIH PHS398 detail budget
5. Budget justification using NIH PHS398 budget justification
6. Current and pending funding including any overlap in funding
7. CV’s for all key personnel

Applications should be sent to Adriana Kuiper, ASU PS‐OC Project Manager, at email hidden; JavaScript is required.

Responsibilities of Awardees:
Awardees will be responsible for presenting at the sponsor site visit and the Center Advisory Committee meeting. They will also need to submit progress reports semiannually. Any publications generated as a result of funding should acknowledge the funding group, NCI PS‐OC, and grant number, U54CA143862.
Evaluation Criteria:
Significance and Impact
-Does the project address an important question in cancer research with a physical sciences perspective that could have a significant impact in the field?
Alignment with ASU PS‐OC Aims
-Do the proposed aim(s) align with the current aims of the ASU PS‐OC?
Scientific Approach and Feasibility
-Does the strategy, methodology, and reasoning seem reasonable and appropriate?
Budget and Justification
-Is the requested budget realistic for the work proposed?

Speaker: Davis Agus, M.D, is an internationally renowned oncologist who holds the position of Professor of Medicine at the University of Southern California. A true visionary, he has become known as an incisive commentator on cancer research and clinical practice.

Location: NEEB Hall

Date & Time: February 29th, 2012 7:00 pm

Title: The End of Illness

Abstract: Dr. Agus proposes a new “systemic” model of health that will dramatically change not only how we take care of ourselves, but also how we spur the next generation of treatments and, in some instances, cures. It’s like that old saying of having to go to war in order to understand peace. His war on cancer in particular has given him a rare and unique vantage point that he has used to develop this different way of honoring the body’s preferred way of life. His ultimate goal is to teach people how to stave off illness and save their own lives through the tactical strategies of personalized medicine and practical prescriptions that are tailored to their specific needs and bodies.

Beyond Center

Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

480.965.3860 | Fax: 480.965.6362

If you have any questions, please contact Amanda Wilber
email hidden; JavaScript is required