Top Stories - Bioinformatics & Systems Biology

Crystal Structure of Anthrax Lethal Factor complexed with a small molecule inhibitor
10 years of science &...

As the United States pauses to observe the 10th anniversary of the September 11th terrorist attacks,...

blood serum
Witnessing the birth of a new...

Sanford-Burnham’s 33rd annual symposium launched an entirely new field of science: Structural...

Dr. Jorge Moscat and Dr. Maria Diaz-Meco
Fueling cancer cell growth

May is National Cancer Research Month, created by Congress in 2007 to recognize the American...

10 years of science & counterterrorism

by on September 11, 2011 at 6:41 am | 0 Comments
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Crystal Structure of Anthrax Lethal Factor complexed with a small molecule inhibitor

Crystal Structure of Anthrax Lethal Factor complexed with a small molecule inhibitor

As the United States pauses to observe the 10th anniversary of the September 11th terrorist attacks, we reflect on the research advances that contribute to new counterterrorism measures—understanding anthrax, for example—and the health of our soldiers in Iraq and Afghanistan, including under-studied conditions such as traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Here are a few examples, and these only cover discoveries made at Sanford-Burnham since September 11, 2001. Can you think of more? Please share your thoughts in the comments below.

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Witnessing the birth of a new scientific field

by on June 14, 2011 at 1:04 pm | 1 comment
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blood serum

Dr. Arthur Olson, of the The Scripps Research Institute, shared this image, which models the complement of proteins and other molecules in blood serum. Dr. Olson's lab uses animation techniques normally found in blockbuster movies to make these sophisticated models. Image courtesy of TSRI's Molecular Graphics Laboratory.

Each year, Sanford-Burnham’s annual symposium features a different topic. Past years have focused on infectious diseases, RNA biology and other disciplines. This year, however, the 33rd annual meeting introduced an entirely new scientific field: Structural Systems Biology.The June 7 symposium was opened with a welcome from Dr. Adam Godzik, director of Sanford-Burnham’s Bioinformatics and Systems Biology Program and one of the meeting’s co-organizers. “When I tell people I am a biologist, they think of organisms,” he said, showing a picture of zoo animals and wildflowers. “But I actually work on the parts.” With that, he flipped to cartoons of genes and proteins.

Structural Biology generates data related to the physical shape of these individual proteins– how they’re folded, how they form complexes with other proteins, what they look like in 3D. That information helps answer questions about how proteins perform their duties –facilitate chemical reactions, carry molecular signals in and out of cells, control cellular movements, etc. Understanding a protein’s structure and function helps identify its role in human health and disease, as well as its potential as a therapeutic target.

But, as Dr. Godzik went on to explain, these individual components all exist as part of a system. They are each a “node” in a network that controls an aspect of cellular behavior – turning genes on and off, communicating with other cells, metabolizing nutrients or performing any number of other processes. Systems Biology focuses on all these components and the interactions among them. Scientists in this field aim to create meaningful models capable of quantifying and predicting these complex cellular processes.

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Fueling cancer cell growth

by on May 17, 2011 at 8:00 am | 2 Comments
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Dr. Jorge Moscat and Dr. Maria Diaz-Meco

Dr. Jorge Moscat and Dr. Maria Diaz-Meco

May is National Cancer Research Month, created by Congress in 2007 to recognize the American Association of Cancer Research (AACR) for its contributions to the field. To honor AACR and highlight some of the important cancer research being done at Sanford-Burnham, we will be posting a series of articles on the ongoing work in our National Cancer Institute-designated Cancer Center. The vast majority of this research is made possible by funding from the National Institutes of Health (NIH), which includes the National Cancer Institute (NCI).

Fifty years ago, cancer biologists were convinced that understanding cancer metabolism would lead to a cure, until discoveries about cancer genetics shifted the research focus in other directions. But now the pendulum is swinging back , renewing interest in metabolism’s role in cancer.

Dr. Jorge Moscat and Dr. Maria Diaz-Meco, who both recently arrived at Sanford-Burnham from the University of Cincinnati, have been working together for more than twenty years to understand the mechanisms that allow cancer cells to grow at such a breakneck pace. Their investigations have led them to a network of proteins characterized by having PB1 domains. This  network of proteins controls inflammation, how cells communicate with each other, and how they sense nutrients—all key drivers of cancer growth.

For example, the PB1-containing scaffold protein p62 regulates an enzyme called protein kinase C zeta (PKCZ), which is often missing in human cancers. PKCZ is a tumor suppressor that prevents inflammation and ensures that cells remain sensitive to nutrient levels. Cells without PKCZ get reprogrammed to endure food scarcity.

“If they lack this gene, they don’t care if glucose is unavailable,” says Dr. Moscat, “they just use other nutrients.”

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Systems Biology: anatomy of a network

by on May 13, 2011 at 6:00 am | 0 Comments
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Sanford-Burnham will be hosting a symposium on Structural Systems Biology on June 7

Sanford-Burnham will be hosting a symposium on Structural Systems Biology on June 7

People often say that a city is like a living organism. Sanford-Burnham researchers are taking this analogy literally and developing new approaches to understanding problems in biology and medicine – systems biology. A single street isn’t that complicated – cars simply drive up and down. But the system gets much more complex when you add hundreds or thousands of vehicles, intersections, lights and intricate traffic rules. That’s when you get a lot of “non-local” effects. Repairs on one section of highway motivate drivers to choose alternate routes, which creates a traffic jam in a different part of town.Traditionally, researchers sought to understand isolated aspects of a cell’s biology.What does this protein look like? What does it do? This was a bit like trying to understand a city’s unique traffic patterns by separately studying individual streets. Systems biology takes a more holistic approach, attempting to understand the larger picture of how all (or most) of the components in a cell or organism function together. Dr. Adam Godzik, who directs Sanford-Burnham’s Bioinformatics and Systems Biology Program, is one of several researchers leading the way towards this “big picture” understanding.

“We have 20,000 genes in any given cell and at any given moment 7,000 of them will be transcribed and translated into proteins,” says Dr. Godzik. “And there is something like several million proteins in a cell. So how do we describe systems like this?”

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Leaders among peers

by on April 29, 2011 at 9:32 am | 0 Comments
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Wordle archive

Sanford-Burnham scientists are leading several exciting symposia over the next few months. Please follow the links below for more event and registration information.

2011 Signaling, Metabolism and Hypoxia Symposium
Chaired by Dr. Ze’ev Ronai
May 6, 2011, 2:00 – 5:30 p.m. (PDT)
Sanford-Burnham Medical Research Institute
10901 North Torrey Pines Road
La Jolla, California

2011 Glycobiology Gordon Research Conference
Chaired by Dr. Hudson Freeze
May 8 – 13, 2011
Il Ciocco Hotel
Lucca (Barga), Italy

Sanford-Burnham’s 33rd Annual Symposium: Structural Systems Biology
Chaired by members of the Bioinformatics and Systems Biology Program
Drs. Adam Godzik, Dorit Hanein, Andrei Osterman, Niels Volkmann
June 7, 2011, 9:00 a.m. – 5:15 p.m. (PDT)
Hilton La Jolla Torrey Pines
La Jolla, California

Cardiomyocyte Regeneration and Protection
Chaired by Dr. Mark Mercola
Sponsored by Abcam
June 20 – 21, 2011
Hilton La Jolla Torrey Pines
La Jolla, California

2011 Molecular Therapeutics of Cancer Research Conference
Chaired by Dr. Sara Courtneidge
Sponsored by the Cancer Molecular Therapeutics Research Association
July 10 – 14, 2011
Asilomar Conference Center
Pacific Grove, California

Seventh General Meeting of the International Proteolysis Society
Chaired by Dr. Guy Salvesen and Dr. Matthew Bogyo
October 16 – 20, 2011
Hilton San Diego Resort and Spa
San Diego, California

Seeing is believing

by on April 6, 2011 at 10:01 am | 1 comment
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Left: traditional electron microscopy view of actin filaments. Right: Dr. Dorit Hanein's 3-D view of actin.

Left: electron microscopy view of actin. Right: Dr. Dorit Hanein's 3-D view.

Life is complicated. Even one tiny cell has a lot going on at any given time, even when things are running smoothly. Normal cellular functions and their emergency responses (like to injury or infection) are mostly carried out by proteins. Proteins tell other proteins what to do by carrying signals, tagging one another with chemical groups, chewing up other proteins or helping assemble new ones, and so on. They also help orchestrate which genes are turned on or off and when.

The cell itself is constantly sensing and reacting to constant environmental fluctuations, as are the individual proteins and other molecules. So how do you connect these two things?

“You can see a cell by eye, using a standard microscope. But you can’t see individual molecules that way,” explains Sanford-Burnham’s Dr. Dorit Hanein. “A cell is on the micrometer scale (one-thousandth of a millimeter), while an individual molecule is on the nanometer scale (one-millionth of a millimeter). That’s like the difference between walking the 500 miles from here [San Diego] to San Francisco, versus walking from here to the moon.”

What Dr. Hanein and other scientists need are techniques that allow them to look not just at the moon, but at the earth, the moon and everything in between.

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Writing the book on protein structure

by on March 24, 2011 at 10:40 am | 1 comment
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Protein structures, like these from the bacterium Thermotoga maritima, help us understand both the form and function of protein networks.

Protein structures, like these from the bacterium Thermotoga maritima, help us understand both the form and function of protein networks.

Whether online or in print, a scientific paper typically winds up sandwiched between two equally important – but completely unrelated – articles. But a scientific journal called Acta Crystallographica Section F recently did something completely different. They ran an issue entirely devoted to research from a single group – the Joint Center for Structural Genomics (JCSG), one of the NIH’s Protein Structure Initiative centers. JCSG is led by Dr. Ian Wilson at The Scripps Research Institute, with Dr. John Wooley at UC San Diego and Sanford-Burnham’s Dr. Adam Godzik leading the bioinformatics and data management part of the project.It’s unusual for a journal to dedicate an entire issue (35 papers total) to one research group, but that’s not the only thing that made this unique.

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Quick peek at Sanford-Burnham

by on March 23, 2011 at 7:19 am | 0 Comments
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Sanford-Burnham's La Jolla campus. Photo by Nadia Borowski Scott

A video by high school student Daniel Osterman, son of Sanford-Burnham investigator Dr. Andrei Osterman, takes a quick look at the basic biomedical research being conducted at the Institute. In particular, the piece focuses on Dr. Hudson Freeze’s research. Dr. Freeze recently organized Sanford-Burnham’s 2nd Annual Rare Disease Symposium, and studies a group of rare conditions called Congenital Disorders of Glycosolation (CDG), in which sugars fail to attach properly to proteins.

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Crowdsourcing science with TOPSAN

by on January 10, 2011 at 10:43 am | 3 Comments
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New advances in technology are allowing scientists to sequence genomes and determine the structures of the proteins they encode at a faster rate and lower cost than ever before. The NIH’s Protein Structure Initiative centers, such as the Joint Center for Structural Genomics (JCSG), have been instrumental in establishing the structures of hundreds of proteins each year. While this flood of new data is a boon to science, the time and resources needed to analyze it all has become a major bottleneck.

“We have become victims of our own success,” explains Dr. Adam Godzik, director of the Bioinformatics and Systems Biology program at Sanford-Burnham. “New protein structures are being determined all the time. And while it’s important to know what a protein looks like, we need to better leverage that information to improve our understanding of how a protein works and what biological functions it performs in a cell.” Moreover, knowledge of a protein’s structure and function is necessary for identifying its role in human health and disease, as well as unveiling its potential as a therapeutic target.

Several years ago, Dr. Godzik and his research team came up with an idea to “crowdsource” protein structure annotation. In 2006, along with their JCSG colleagues, they launched The Open Protein Structure Annotation Network (TOPSAN), a central portal for scientists to collect, share and distribute information about three-dimensional protein structures. TOPSAN embodies the idea that many can succeed where the individual cannot. No matter how much any one person knows about a particular protein, there are others in the scientific community who know more about other aspects of the same protein. Thus, the collective analyses from multiple experts around the world are far more informative than the localized information that any one individual – or even single research group – could contribute.

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Some like it sweet

by on May 28, 2010 at 10:23 am | 0 Comments
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Bacteria need sugars to survive. So they grab sugars where they can – either by making them or by taking them up from the environment – and mold them into a form that can be used nutritionally (to make energy) or structurally (to build a cell wall, for example). In turn, a bacterial cell’s sugar give-and-take can influence its environment, whether that’s water, soil or the human gut. With the long-term goal of developing ways to manipulate bacteria for a desired outcome, like new antibiotics or producing alternative energy, scientists are piecing together the complicated machinery that bacteria use to modulate sugars. In doing so, they face the major challenge of figuring out which genes are involved and what roles they play in sugar processing.

Sanford-Burnham’s Dr. Andrei Osterman addressed this problem in a talk he gave last week at the San Diego Consortium for Systems Biology’s 5th Annual Systems to Synthesis symposium, held at the Salk Institute for Biological Studies. Two types of bacteria that Dr. Osterman uses to study sugar processing pathways, Thermotoga maritime and Shewanella oneidensis, may have potential industrial applications to produce biohydrogen or clean up nuclear waste.

Early in his talk, Dr. Osterman summed up his group’s method for pinpointing what a gene does. “Coming from Russia, I think of it as a very American approach,” he joked. “We try to figure out what’s going on by taking a look around the neighborhood.”

He means the genomic neighborhood, of course.

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