The Center for Biosignatures Discovery Automation at Arizona State University’s Biodesign Institute seeks to fill a Postdoctoral Research Fellow position in single-cell CT imaging research.  The project (a component of a funded PSOC, Physical Sciences in Oncology Center at ASU, see http://beyond.asu.edu/Cancer/index.php) focus is on further development of a new method, called cell CT, for 3D imaging of biological cells.  Our overarching objective is to better understand relationships and correlations between cellular genome, transcriptome, structure and function.  The cell CT produces 3D images of cells from transmitted or emitted optical pseudoprojections.  We call the raw data “pseudoprojections” since it is formed by scanning the focal plane through the specimen at each of hundreds of angular orientations.  We use filtered backprojection and other methods to recover the 3D object function from the raw data.

We seek an energetic scientist with significant depth and experience in image reconstruction from projections, preferably for micro-CT.  Transmission and emission tomography are both utilized in our research.  A PhD in engineering, physics, mathematics, computer science, or other appropriate discipline is required.  The successful candidate must have the demonstrated ability to conceive and implement (either by coding in a standard computer language or by use of an environment like Matlab or Mathematica) standard and novel image reconstruction algorithms.  Hands-on experience with algorithm implementation is an absolute requirement for the position.  Experience with various approaches, including filtered backprojection, analytical (iterative), Fourier, and statistical methods is preferred.  The ability to conceive innovative methods and implement algorithms for such ancillary tasks as projection alignment and object motion estimation is required.

Previous practical, hands-on experience with laboratory micro-CT or optical microscope systems is preferred, but not required.  Background in optics and optical system conception, design and implementation is desirable.  A record including peer-reviewed publications is highly desirable.  In addition to research and designing experiments, the successful candidate is expected to be involved in proposal writing and student mentoring activities.  Excellent writing and communication skills and the ability to function as a member of a multidisciplinary team are essential.  Salary and benefits are competitive.  The position is renewable annually for a maximum of three years, contingent on satisfactory performance, availability of funding, and the needs of the program.

This position was posted in June 2010, and remains open as of Feburary 22, 2011.  The application deadline is July 15, 2010, or every two weeks thereafter until the position is filled.  Qualified individuals should send a cover letter, curriculum vitae and provide contact information (e-mail and telephone numbers preferred) for three professional references to: Roger H. Johnson, Ph.D., Research Lab Manager, Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ  85287-6501. The cover letter should detail (several paragraphs) the candidate’s specific, hands-on experience in coding of reconstruction algorithms.  Materials should be sent as a PDF file attached to an email, with “PSOC Postdoc” in the subject line, to email hidden; JavaScript is required.

Arizona State University and Translational Genomics Research Institute

DETAILED DESCRIPTION:

This position involves design and execution of descriptive studies of the genomic, biochemical, and stoichiometric properties of tumor cells and tissues. The postdoc will work in characterizing genomic data of diverse tumor types, performing biochemical (RNA, DNA) and elemental (C, N, P) analysis of tumor cells and tissues, and integrating these data into bioinformatic and evolutionary frameworks. The Postdoctoral Fellow will work closely with the Senior Investigators (Berens, Barrett at TGEN, along with ASU Regents’ Professor Jim Elser) on peer-reviewed and new projects that involve co-investigators within TGen and at outside institutions. The Fellow will assume progressively more autonomous responsibilities for project development and execution with the aim of career maturation towards being an independent (extramurally-funded) scientist. The Fellow will assist in manuscript preparation, grant proposal development, scientific presentations and progress reports.

ESSENTIAL FUNCTIONS:

Projects in the laboratory include cancer-centric investigations that require competency, proficiency, and/or familiarity with (the majority of) the following: Experimental design, technical execution, data analysis, interpretation, and presentation of findings from studies using genomic techniques including DNA sequencing, gene expression profiling, gene promoter CgP island methylation, comparative genomic hybridization (CGH), and qRT-PCR; standard laboratory methods for tissue processing for isolation of DNA, RNA, and protein, plasmid design and construction, siRNA and transfection experiments; Experimental design, technical execution, data analysis, interpretation, and presentation of findings from in vitro cell biology studies of mammalian cell proliferation, apoptosis, migration, and viability; Experimental design, technical execution, data analysis, interpretation, and presentation of findings from studies on biochemical analysis using spectrophotometric and fluorometric means of nucleic acid and protein quantification; Study design, technical execution, data analysis, interpretation, and presentation of findings from bioinformatics of gene expression profiling and comparative genomics; Familiarity with electronic communication (word processing, spreadsheet, presentation software), manuscript development, grant proposal preparation;

ADDITIONAL FUNCTIONS:

Participate in lab meetings and other scientific activities to enhance collaborative relationships among ASU and TGEN researchers, including the lead PIs and ASU’s PSOC program. Participate in institute tours, representing the research program and the ongoing progress of TGen to interested groups (typically lay audiences).
Job Requirements: Ph.D. in related field of research

To apply:

Send cv, statement of research accomplishments and interests, and list of three referees to Jim Elser (email hidden; JavaScript is required)

More Info:

Lab web site: http://www.elserlab.asu.edu/index.html | Dept web site: http://sols.asu.edu/faculty/jelser.php

A hallmark of cancer is that the cell nucleus changes shape and size as the cell transforms from healthy to premalignant to malignant, and cancer researchers suspect that an accurate method of quantifying those changes could serve as an early diagnostic test for cancer. Now, a team of investigators at Arizona State University have given cancer researchers an imaging tool that should enable them to determine if that suspicion is correct.

Deirdre Meldrum and Roger Johnson, both members of the Arizona State University Physical Sciences-Oncology Center (PS-OC), led the team that used high-resolution optical absorption tomographic imaging and mathematical reconstruction to create detailed three-dimensional images of the cell nucleus. They then took those images and used an automated analytical technique they developed to compute 41 quantitative descriptions of a cell’s nuclear structure. The investigators also developed mathematical tools to quantify the spatial distribution of DNA within the cell nucleus from the reconstructed optical images.

Using these techniques, the Arizona PS-OC team compared the three-dimensional architecture of malignant, premalignant, and malignant esophageal epithelial cells and identified quantitative differences in cell shape among the three cell types. Moreover, the researchers were able to clearly distinguish between the three different types of cells using those quantitative measures. The researchers published the results of their study in the journal Cytometry Part A.

This work, which is detailed in a paper titled, “Quantitative Characterization of Preneoplastic Progression Using Single-Cell Computed Tomography and Three-Dimensional Karyometry,” was supported by the National Cancer Institute’s Physical Sciences-Oncology Centers program that aims to foster the development of innovative ideas and new fields of study based on knowledge of the biological and physical laws and principles that define both normal and tumor systems. An abstract of this paper is available at the journal’s Web site.

NandakumarCytometryA2011
source: http://physics.cancer.gov/news/2011/jan/po_news_a.asp

Gaurav Sharma

Location: John W. Schwada Building

Date & Time: Friday February 25th, 2011 1:30 p.m.

Web Cast: Unavailable

Summary:
Macrophages are versatile plastic cells that are key components of the body’s immune system. The interaction of engineered nanoparticles with macrophages is important because these cells clear nanoparticles from the circulation, and because they are potential therapeutic targets in inflammatory conditions, atherosclerosis and cancer. Therefore, an understanding of the features of engineered nanoparticles that influence their interaction with macrophages may allow optimization of their properties for enhanced drug delivery and imaging.
In the first part of this talk I will present results from a study where I showed that particle shape impacts phagocytosis by macrophages, and more importantly, that particle shape and size separately impact attachment and internalization. The study provides methodology for further exploring how particle shape can be controlled to achieve desired attachment and internalization. The results of the study also give mechanistic guidance on how particle shape can be manipulated to design drug carriers to evade macrophages, or alternatively to target macrophages.
In the second part, I will present results from a study where I investigated an alternate therapy for cancer by targeting and killing tumor associated macrophages (TAMs) that promotes tumor growth and metastasis. For this project, I designed nanoparticles that are loaded with an anti-macrophage drug and are actively targeted to TAMs in a mouse model of tumor and showed that these nanoparticles can selectively abrogate TAMs which leads to a suppression in tumor growth.

Thank you and if you have questions please contact Kaushal Rege, Assistant Professor of Chemical Engineering.
Email: email hidden; JavaScript is required Phone: 480-727-8616

Josh Labaer

Speaker: Josh LaBaer,Ph D. Directory, Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University.

Location: Biodesign Auditorium

Web Cast: View Web Cast Video

Date & Time: Feb. 24th, 2011 12:00 p.m.

Title:High Throughput Cell-Based Studies and Protein Microarrays for Biomarker and Target Discovery
Summary:
One of the most compelling steps in the post-genomic era is learning the functional roles for all proteins. We have developed the FLEXGene Repository (for Full-Length Expression-ready), which comprises over 8000 full length clones for human genes, as well as complete genomes collections for several microorganisms enabling the high-throughput (HT) screening of protein function for the entire set (or any customized subset) of genes using any method of in vitro or in vivo expression.
The clones from the repository can be rapidly incorporated in HT biological experimentation. Using HT retroviral methods, proteins capable of inducing cancer-like behavior and conferring drug resistance can be tested. We derived a series of sub-cloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones that also predicts disease-free survival in tamoxifen treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicts poor clinical outcome in patients. Further studies revealed that HSPB8 protects MCF7 cells from tamoxifen and blocks autophagy. Moreover, silencing HSBP8 induces autophagy and causes cell death.

Click the slide above to view the presentation online

We developed a novel form of protein microarray, called nucleic acid programmable protein array (NAPPA). In lieu of producing and printing purified proteins, this method substitutes the printing of cDNAs encoding the proteins. Thus, the resulting array is a DNA array that can be converted into a protein array by adding cell free protein synthesis machinery. This obviates the need to purify proteins, produces human proteins in a mammalian milieu, and avoids concerns about protein stability on the array because the proteins are made just-in-time for assay. Moreover, the method displays a broad variety of proteins, insensitive to protein class or size with a high yield of protein per feature while maintaining a narrow range of protein yield from protein to protein.
NAPPA arrays can be used to study protein-protein interactions, protein-drug interactions, search for enzyme substrates, and as tools to search for disease biomarkers. In particular, recent experiments have focused on using these protein microarrays to search for autoantibody responses in cancer patients. Several bona fide autoantibody responses, such as responses to p53, have been detected, and a pilot study of responses to 7500 full length human proteins in 50 breast cancer patients and 50 controls has identified over 700 candidate proteins with more frequent responses in patients. These experiments show promise in finding antibody responses that appear in only cancer patients.

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

Vanessa Baack, 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

Speaker: Joseph Mikhael, MD, consultant hematologist at the Mayo Clinic in Scottsdale.

Location: Biodesign Auditorium

Web Cast: View Web Cast Video

Date & Time: March 24th, 2011 12:00 p.m.

Summary:

Dr. Mikhael’s’ primary research interests are in multiple myeloma and related conditions.

Click Slide Above to view presentation online (https://breezemeeting.asu.edu/p13982316/)

Thank you and if you have questions please contact Vanessa Baack!

Vanessa Baack, 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

Two scientists, including ASU’s Paul Davies, write about the idea that cancer has ancient evolutionary roots in a paper released Feb. 7 in the journal Physical Biology. Davies heads up the Center for the Convergence of Physical Sciences and Cancer Biology at ASU, a major research initiative funded by the National Cancer Institute. His center is investigating insights from physical science on cancer cells, similar to the ones in this image. Shown here, the upper row shows a normal breast cell with a smooth nuclear membrane of regular shape. The bottom row shows an aggressive breast cancer cell with a distinctively irregular nucleus and overall shape. The left column shows the whole cell, with the cytoplasm appearing as a gray haze. The middle column shows the naked nuclear membrane and the right column shows density variations in the nuclear DNA. (Image courtesy of Vivek Nandakumar, Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University)

Now available, an interview with article co-author Charles Lineweaver. Read Now

Despite decades of research and billions of dollars, cancer remains a major killer, with an uncanny ability to evade both the body’s defenses and medical intervention. Now an Arizona State University scientist believes he has an explanation.

“Cancer is not a random bunch of selfish rogue cells behaving badly, but a highly-efficient pre-programmed response to stress, honed by a long period of evolution,” claims professor Paul Davies, director of the BEYOND Center for Fundamental Concepts in Science at ASU and principal investigator of a major research program funded by the National Cancer Institute designed to bring insights from physical science to the problem of cancer.

In a paper published online Feb. 7 in the UK Institute of Physics journal Physical Biology, Davies and Charles Lineweaver from the Australian National University draw on their backgrounds in astrobiology to explain why cancer cells deploy so many clever tricks in such a coherent and organized way.

They say it’s because cancer revisits tried-and-tested genetic pathways going back a billion years, to the time when loose collections of cells began cooperating in the lead-up to fully developed multicellular life. Dubbed by the authors “Metazoa 1.0,” these early assemblages fell short of the full cell and organ differentiation associated with modern multicellular organisms – like humans.

But according to Davies and Lineweaver, the genes for the early, looser assemblages – Metazoa 1.0 – are still there, forming an efficient toolkit. Normally it is kept locked, suppressed by the machinery of later genes used for more sophisticated body plans. If something springs the lock, the ancient genes systematically roll out the many traits that make cancer such a resilient form of life – and such a formidable adversary.

“Tumors are a re-emergence of our inner Metazoan 1.0, a throwback to an ancient world when multicellular life was simpler,” says Davies. “In that sense, cancer is an accident waiting to happen.”

If Davies and Lineweaver are correct, then the genomes of the simplest multicellular organisms will hide clues to the way that cancer evades control by the body and develops resistance to chemotherapy. And their approach suggests that a limited number of genetic pathways are favored by cells as they become progressively genetically unstable and malignant, implying that cancer could be manageable by a finite suite of drugs in the coming era of personalized medicine.

“Our new model should give oncologists new hope because cancer is a limited and ultimately predictable atavistic adversary,” says Lineweaver. “Cancer is not going anywhere evolutionarily; it just starts up in a new patient the way it started up in the previous one.”

The authors also believe that the study of cancer can inform astrobiology. “It’s not a one-way street,” says Davies. “Cancer can give us important clues about the nature and history of life itself.”

ASU SOURCE:
Paul Davies, email hidden; JavaScript is required

ANU SOURCE:
Charles Lineweaver, email hidden; JavaScript is required

ASU MEDIA CONTACT:
Carol Hughes, email hidden; JavaScript is required
480-965-6375/office, 480-254-3753/cell

ANU MEDIA CONTACT:
Stephen Watt, email hidden; JavaScript is required

Originally posted on: ASU NEWS