Top Stories - Infectious Diseases

Structure of bacterial flagellin bound to TLR5
How the body fends off...

A team led by scientists at Sanford-Burnham and Scripps Research develop the first 3D look at...

Dr. Jaime Green
Basic research bolsters...

While treating bone marrow transplant patients in the clinic, Dr. Jaime Green became concerned about...

Dr. Tariq Rana
Hibernating herpes viruses

Herpes viruses are good at hiding. They infect human cells and lay dormant there until replication...

Dr. Carl Ware
Carl Ware & secrets of...

Dr. Carl Ware has joined Sanford-Burnham’s faculty as Director of the Infectious and...

Assembling to attack infection

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Each day, we are confronted by millions of bacteria, all attempting to invade our bodies and cause infection. It’s the job of the body’s immune system to defend against these little invaders. In order to fight off bacteria (as well as viruses and cancerous cells), the immune system has an arsenal of weapons at its disposal. One of these weapons is the complement system. Complement is so important for fighting infections that people who have mutations in certain complement proteins or their regulators often suffer from frequent bacterial infections.

How the body fends off bacteria

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To invade organisms such as humans, bacteria make use of a protein called flagellin, part of a tail-like appendage that helps the bacteria move about. Now, for the first time, a team led by scientists at The Scripps Research Institute and Sanford-Burnham Medical Research Institute has determined the 3D structure of the interaction between this critical bacterial protein and an immune molecule called TLR5, shedding light on how the body protects itself from such foreign invaders.

The study, published February 17 in Science, not only helps decipher the molecular mechanism underlying TLR5 recognition and function, but it also advances knowledge that’s key to the design of new therapeutics.

World Health Day 2011: No Action Today, No Cure Tomorrow

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Editor’s update, April 8, 2011: It’s not too late – you can still find audio and slides from this event here.

Today, World Health Day 2011, the World Health Organization (WHO) calls on governments and stakeholders to implement the policies and practices needed to prevent and counter the emergence of microorganisms resistant to current therapies.

Antibiotics are among the most important advances in human health, but their use and misuse over the past 70 years have increased the number and types of microorganisms resistant to antibiotics – resulting in deaths, greater suffering and disability and higher healthcare costs. The challenge posed to the pharmaceutical and biotechnology industries is loud and clear – only seven new antibiotics have been introduced since 2003.

A press conference will be held this afternoon at Sanford-Burnham’s La Jolla, Calif. campus to feature innovators in antibiotic research and development.

WHAT: Innovation in Antibiotics: Medicine for the Next Wave of Bacterial Infections

WHEN: Thursday, April 7, 2011 at 2:00 p.m. – 3:00 p.m. U.S. Pacific Time

WHERE: Sanford Children’s Health Research Center, Sanford-Burnham Medical Research Institute, 10905 Road to the Cure, San Diego, CA 92121 or via webcast.

Quick peek at Sanford-Burnham

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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.

Basic research bolsters clinical care

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Bone marrow (stem cell) transplants have been a life-saving tool for patients with leukemia and lymphoma. However, like most cancer treatments, they come with significant risk. Patients can be immune-compromised for as long as a year, making them vulnerable to pathogens that most people would fight off easily.

One such pathogen is cytomegalovirus (CMV), a member of the herpes virus family. People usually get CMV early in life (from childhood to early adulthood), experience mild symptoms and move on. However, for immune-compromised patients, CMV can be a serious and deadly complication.

High-impact research

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Two years ago, Sanford-Burnham’s Dr. Sumit Chanda, Salk’s Dr. John Young and colleagues collaborated on a paper about HIV infection. They were trying to figure out how the virus, with only nine genes that code for 15 proteins, could be so effective with such a small genetic payload. They knew the virus was hijacking human proteins to succeed, but they wanted to pinpoint exactly which proteins were affected. The study, published October 3, 2008 in Cell, identified 295 host proteins involved in HIV infection. Since then, these findings have greatly impacted HIV research. In recognition of the paper’s significance, Thomson Reuters’ Science Watch has named it a “Fast Moving Front” paper for January 2011. In the accompanying interview with Science Watch, Drs. Chanda and Young said:

This was one of the first studies to combine genome-wide RNAi screening and bioinformatics to identify the repertoire of host cellular factors that help facilitate HIV replication in human cells. It represents a significant advance in our understanding of viral-host interactions, providing a blueprint of the machinery that is exploited by the virus.

The paper’s ripple effect is likely to continue - researchers are just now beginning to develop anti-HIV therapies that target some of these 295 host proteins.

Our Top 10 of 2010

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As 2010 comes to a close, we take a look back at our top 10 most popular posts here on Beaker, the Sanford-Burnham science blog. Enjoy… and have a Happy New Year!

  1. DNA 101
  2. Diabetes Meeting Adds Human Element to Research
  3. Students in Lab Coats
  4. Academia Jumps into Drug Discovery
  5. Big Boost for HIV Research
  6. A Balance of Fat and Sugar
  7. Congresswoman ‘Inspired’ by Center for Nanomedicine
  8. Molecular Dominoes Tip Tumors toward Metastasis
  9. Putting the Muscle in Muscle Stem Cells
  10. Acting Locally

(This post is our December entry in the Health Activist Blog Carnival. Read all about it here.)

Fresh recruits at the immunological frontlines

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The immune system is always standing by, ready to fight infection. Immune cells called lymphocytes and dendritic cellshang out in lymph nodes, surveying the environment for signs of invaders and attacking infected cells when necessary.“It’s crucial that lymphocytes meet dendritic cells in the confined space of a lymph node – they’d have a hard time finding one another in the fast-moving bloodstream,” explains Dr. Minoru Fukuda, professor in Sanford-Burnham’s NCI-Designated Cancer Center.

Dr. Fukuda, along with staff scientist Dr. Xingfeng Bao and their colleagues, recently showed that heparan sulfate – a type of long sugar chain – is responsible for recruiting these immune cells to their lymph node meeting places. Normally, lymphocytes flow through the bloodstream until blood vessel cells rope them in. From there, the immune defenders can squeeze out of the blood stream and into the surrounding tissue or lymphatic system.

Hibernating herpes viruses

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Herpes viruses are good at hiding. They infect human cells and lay dormant there until replication is activated by stress or some other environmental factor. One type, Kaposi’s sarcoma-associated herpesvirus (KSHV), is one of only a few viruses known to cause cancer.

In a study that appeared online September 17 in the journal EMBO Reports, Sanford-Burnham’s Dr. Tariq Rana and colleagues found that KSHV stays quiet by expressing certain microRNAs (miRNAs), small strands of genetic material that interfere with protein production.

“KSHV dormancy is believed to be essential for tumor formation, yet some forms of cancers caused by the virus have also been linked to viral reactivation,” explains Dr. Rana, professor and director of Sanford-Burnham’s RNA Biology Program. “This study helps us better understand the KSHV life cycle, thus providing new insight into how the virus causes cancer in some populations.”

Carl Ware & secrets of the immune system

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Dr. Carl Ware has joined Sanford-Burnham’s faculty as Director of the Infectious and Inflammatory Disease Center (IIDC). Although, this is the first time Dr. Ware has been employed at Sanford-Burnham, his roots with the Institute go back to 1996. That’s  when he, Dr. John Reed, Dr. Guy Salvesen and others began a collaborative project to study apoptosis and cell death. That same year, Dr. Ware joined the La Jolla Institute for Allergy and Immunology, where he led the Division of Molecular Immunology. Over the years, he has maintained strong ties with Sanford-Burnham.Dr. Ware’s research focuses on the fundamental pathways that control cytokines, a family of proteins involved in immune signaling. One group of cytokines, called tumor necrosis factors or TNF, are part of an intricate communication network between immune system cells.

“They’re complicated circuits,” says Dr. Ware. “There are more than two dozen proteins in this family and an equal number of receptors. The pathways involve hundreds of proteins. In infectious disease, these pathways are amplified in a very dramatic fashion. In autoimmune disease the pathways escape regulatory control entirely. Something just goes haywire. However, with any circuit, theoretically, you can rewire around it.”

Influenza and nanomachines

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Drs. Sumit Chanda and Erkki Ruoslahti have received write-ups at two very distinct sites. Dr. Chanda’s flu research, which was published in February in Nature, was recently highlighted by the National Institute of Allergy and Infectious Disease, one of the National Institutes of Health. The work, a collaboration with Mount Sinai , Salk and GNF, identified 295 human proteins and other molecules  that influenza A strains must harness to infect a cell.  As the article points out,  the flu virus contains only 11 proteinsand must rely on our own cellular machinery to keep going. In many ways, these host factors may be better targets for treatment.

Current flu drugs are aimed directly at the influenza virus. But the flu virus mutates readily and these frequent changes allow it to gain resistance to antiviral drugs. However, if a drug were to be targeted to factor in the human host instead of being aimed directly at the virus, the pathogen’s ability to escape through mutation would be thwarted.

Meanwhile, Dr. Ruoslahti, who cofounded the Sanford-Burnham, UC Santa Barbara Center for Nanomedicine, was quoted in an article about robots at CNBC. Dr. Ruoslahti has been working with engineers at UC Santa Barbara to create nanorobots to home in on diseased cells.

“At this point, we can increase the activity of any anticancer drug by three fold or better,” he says. “We get more drug to the tumor and that makes a huge difference. If you can increase its concentration, the side effects remain the same, but the effectiveness is higher.”

Soldiers or thugs?

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Sanford-Burnham CEO Dr. John Reed was quoted in a recent article at The Scientist.com that unwinds how the immune system dukes it out with invading pathogens. The article compares our immune response to the Facebook game Mafia Wars, and makes the case that this conflict more resembles an underworld turf battle than a military-style war. Dr. Reed notes that new technologies have helped us reach this enhanced understanding.

“There certainly has been a rapid pace of discovery in the area of the host–pathogen interaction,” agrees cell and molecular biologist John Reed of the Sanford-Burnham Medical Research Institute in La Jolla, Calif. Like many fields in the life sciences, he adds, the quickly advancing field of  “genomics is a big part of that.”

Some like it sweet

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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.

Another look at pandemic flu

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The San Diego-Union Tribune has a nice article today about pandemic flu.  One flu over: Lessons of the H1N1 Pandemic provides some interesting overviews from a number of flu experts on what went right and wrong (and what could yet happen) in the fight against H1N1. Among the experts were Sanford-Burnham researchers Dr. Robert Liddington and Dr. Sumit Chanda, who have both done extensive research on flu.

“We dodged a bullet,” said Sumit Chanda.

Experiments from outer space

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Professor and astronaut Millie Hughes-Fulfordvisited Sanford-Burnham Medical Research Institute at Lake Nona today. She’s been eagerly awaiting this day since Shuttle Discovery returned from space on Tuesday with her experiment on board. Dr. Hughes-Fulford sent her experiment on the 15-day space journey to test how memory cells survive in space and how T-cells are activated.