Basic Research

Florida Department of Health and Sanford-Burnham to kick off collaborative research program

by Patrick Bartosch on April 25, 2012 at 1:30 pm | 0 Comments

The Collaborative Research Grant program will provide Florida scientists with access to our screening center

Last week was a great one for medical researchers across the state of Florida. The state legislature and governor approved funding for the Collaborative Research Grant program between the Florida Department of Health and Sanford-Burnham Medical Research Institute. Starting in July, the program will provide scientists at universities and non-profit institutes throughout Florida with access to Sanford-Burnham scientists and our state-of-the-art technologies for drug discovery. This includes access to the Institute’s Conrad Prebys Center for Chemical Genomics.

Together with the Florida Department of Health, Sanford-Burnham will develop a competitive grant program, based on peer-review that will provide funds for collaborative projects between Florida-based research scientists and Sanford-Burnham’s fully operational, state-of-the-art drug discovery technology center based at Lake Nona.

Drug discovery case study: high-throughput screening of TNAP

by Patrick Bartosch on April 11, 2012 at 11:52 am | 0 Comments

Full Article

Presence of calcium deposits in a mouse aorta, as revealed by alizarin red staining.

Editor’s note: this is the second in a series of posts highlighting drug screening studies in our Conrad Prebys Center for Chemical Genomics. Read the first post here.

Calcification of the medial layer of arteries is increasingly recognized as an important clinical problem. Medial vascular calcification (MVC) is the major cause of morbidity and mortality in generalized arterial calcification of infancy (GACI), and contributes to cardiovascular deterioration in Kawasaki disease (KD), chronic kidney disease (CKD), as well as in diabetes, obesity, and aging. MVC is thought to result from decreased circulating levels of the mineralization inhibitor, inorganic pyrophosphate (PPi).

Researchers at Sanford-Burnham have revealed that the development of MVC in mouse and rat models is accompanied by up-regulation of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme whose primary function is to hydrolyze PPi, and thus, crucial in determining where mineralization occurs. Preliminary data have proven that upregulation of TNAP is sufficient to cause MVC and Sanford-Burnham scientists have developed potent drug-like inhibitors of TNAP.

A “twisted” grand opening ceremony

by Patrick Bartosch on March 29, 2012 at 3:35 pm | 0 Comments

Full Article

TRI grand opening speakers (from left to right): John Reed, Terry Owen, Dan Kelly, Steve Smith, Lars Houmann, Des Cummings, Don Jernigan

“My goal is to cure diabetes,” Steven Smith, M.D., scientific director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI), said boldly at the opening ceremony of the TRI’s new state-of-the-art facility in downtown Orlando on March 27. “We believe that personalized medicine is our best shot at discovering cures for our most serious health problems like diabetes.”

The ceremony’s highlight was the unveiling of a spectacular nine-foot double-helix DNA structure that will be placed at the main entrance of the building, symbolizing the fundamental research being conducted at the TRI, as well as the synergies and collaborations the TRI represents. Selected board members and presenters each added one illuminated “bar,” representing a nucleotide, to the double helix.

“This is one of those rare times when the reality far exceeds the dream,” said John Reed, M.D., Ph.D., CEO of Sanford-Burnham. “The TRI is a wonderful opportunity for our organization, which will bring more and more to life our slogan From Research, the Power to Cure. We’re very excited about this opportunity to take our relationship with Florida Hospital to the next level.”

Why the economy depends on federal funding for medical research

by Patrick Bartosch on February 22, 2012 at 3:03 pm | 0 Comments

Full Article

NIH funding is crucial for medical research

When Sanford-Burnham CEO John Reed, M.D., Ph.D. traveled to Washington, D.C., in early February, he attended a variety of Capitol Hill briefings to discuss the importance of National Institutes of Health (NIH) funding for medical research. He pointed out that NIH grants account for approximately 80 percent of all funding for non-profit medical research institutions in the United States, such as Sanford-Burnham.

NIH grants contribute to the ultimate goal of developing new treatments for diseases and improving the quality of life for millions of Americans and people worldwide. The research supported by these grants also generates U.S. patents that fuel the biotechnology industry and creates thousands of jobs across the nation. NIH funding supports the training of our biomedical research workforce and strengthens the foundation of a 21st century knowledge-based economy.

International Proteolysis Society “cuts it up” in San Diego

by Heather Buschman on October 28, 2011 at 4:38 pm | 0 Comments

Full Article

Dr. Judith Bond (right), professor and department chair at Penn State College of Medicine and president-elect of the Federation of American Societies for Experimental Biology (FASEB), visits a poster at the 2011 International Proteolysis Society meeting.

Scientists from around the world met in San Diego October 16-20 to discuss their work on proteases at the International Proteolysis Society’s bi-annual meeting. The event, organized by Sanford-Burnham’s Dr. Guy Salvesen and Stanford University’s Dr. Matt Bogyo, brought together more than 300 researchers from a wide variety of fields to provide educational, training, and networking opportunities at all levels.

Proteolysis is a basic cellular function in which enzymes (called proteases) cleave other proteins. Sometimes a cell needs proteases to stop an aberrant protein from sending the cell astray. Other times, proteolytic cleavage activates a protein, cutting it free from an anchor that was holding it back. Needless to say, proteolysis needs to be carefully regulated, as it affects everything from cellular movement to cell lifespan.

Autophagy 101

by Bruce Lieberman on September 5, 2011 at 7:34 am | 0 Comments

Full Article

An autophagosome full of degraded old cell parts, as viewed under an electron microscope. (Image by Malcolm Woods, The Scripps Research Institute)

Every well-run house needs someone to clean up the clutter, prune the hedges, and rake up the leaves, even whip up something to eat when the refrigerator is empty. In the life of a cell, those kinds of jobs are handled by an incredible process called autophagy.

Biologists first observed autophagy in the early 1960s as a mechanism by which cells break down their own components and recycle the parts. Autophagy, which literally means “to eat oneself,” is essential to cell survival, particularly when food is scarce.

But there’s a much larger role for autophagy than just helping a cell survive starvation. The process helps cells dispose of malfunctioning parts, clean up clutter, and defend against invading pathogens.

Shared resources, shared successes

by Faculty Contributor on August 8, 2011 at 1:27 pm | 0 Comments

Full Article

Microscope available in Sanford-Burnham's Cell Imaging facility

Editor’s note: This is the first in a series of posts highlighting Shared Resources available at Sanford-Burnham. Future posts will further explore some of the individual capabilities found in these core facilities.

Suppose you’re a new assistant professor just starting your career at Sanford-Burnham, and you need to perform some high-resolution fluorescence microscopy to finish your first big paper as a principal investigator. How do you afford that $400,000 confocal microscope for the key experiments? For that matter, how does anyone afford a $400,000 microscope? Here’s where Shared Resources saves the day. Just down the stairway sits the Zeiss Laser Scanning Confocal Microscope that Sanford-Burnham’s Cell Imaging facility has thoughtfully provided for you. How did you get so lucky?

Taste receptors…in the gut?

by Bruce Lieberman on August 1, 2011 at 5:58 am | 0 Comments

Full Article

Let’s suppose your summer backpacking trip takes a disastrous turn and you’re lost, out of food, and desperate. You think those berries look OK so you swallow them down—even though they’re as bitter as anything you’ve eaten before. It’s not long before you regret ignoring your taste buds and suspect you’ve eaten something poisonous.

Unless you’re a molecular biologist, you’re probably not thinking at that moment about the biochemistry churning in your gut. But a cacophony of cellular signals is actually assembling a second line of defense to keep your digestive system from absorbing toxins into your bloodstream.

Of course, your body doesn’t always win. But Dr. Timothy Osborne’s lab at Sanford-Burnham’s Lake Nona campus has outlined how bitter taste-sensing receptors on enteroendocrine cells in the gut, called T2Rs, automatically kick into gear when confronted with bitter-tasting substances. You might disregard the taste buds in your mouth, but your digestive system knows better and tries to make up for your recklessness.

Science…under the Tuscan sun

by Faculty Contributor on July 21, 2011 at 2:24 pm | 0 Comments

Full Article

Harrison Ford plays a glycobiologist in the movie Extraordinary Measures.

In the movie Extraordinary Measures, Harrison Ford plays a glycobiologist.

If brides and grooms can have destination weddings, then scientists should be able to have destination research conferences. These types of conferences are increasingly popular as opportunities for scientists to experience fun locales while also interacting and exchanging ideas with a relatively intimate group of expert colleagues. The Gordon Research Conferences have been trendsetters with this format since the 1930s, sponsoring scientific meetings on a variety of topics at sites within the U.S. Starting in 1990, Gordon Conferences have been held in more exotic foreign locations, including Italy, Switzerland, Japan, England, Hong Kong… and even Texas.

Earlier this summer, Dr. Hudson Freeze, program director in Sanford-Burnham’s Sanford Children’s Health Research Center, chaired the Gordon Conference on Glycobiology in Lucca, Italy. 170 glycobiologists from around the world gathered to hear about exciting new developments in the science of carbohydrates (sugar molecules) and the complex molecules like proteins and lipids whose properties are influenced by incorporation of carbohydrates. Once a rather understudied area of biology, glycobiology has been transformed by the realization that carbohydrates mediate many of the key molecular interactions that govern cellular function. Meeting topics included the effects of sugar modifications during development, the role of carbohydrates in normal adult physiology and the involvement of carbohydrates in tissue engineering and repair, including their importance in stem cell biology.

Happy Birthday ELISA

by Communications Staff on June 17, 2011 at 1:09 pm | 0 Comments

Full Article

Dr. Eva Engvall a few years after her work on ELISA.

You may never have heard of ELISA, but you have almost certainly been touched by it. Since its creation by Dr. Peter Perlmann and Dr. Eva Engvall at Stockholm University in 1971, ELISA (an acronym for enzyme-linked immunosorbent assay) has been one of the most widely used research and diagnostic tools ever. The purpose of an ELISA is to determine if a particular protein, chemical or pathogen is present in a sample (such as blood or urine) and if so, how much. ELISA was created to help bench scientists with their research, but overachieved in a big way. Consider the sheer variety of conditions ELISA can detect: allergies, HIV, West Nile virus, malaria, blood glucose concentrations, pregnancy, food-borne pathogens, the list goes on and on. Then think about all the technological changes the biological sciences have experienced over the past 40 years—and yet, ELISA remains a laboratory staple.

Image by Jeffrey M. Vinocur

One of ELISA’s appeals is its simplicity. One version of the technique, called the sandwich ELISA, works something like the diagram to the right. 1) First, a plate is coated with “capture” antibodies that will specifically bind the protein of interest. 2) Then, a mixed sample containing the protein is applied. When the excess fluid is rinsed off, just the target proteins bound to antibodies remain. 3) To determine how much protein is there, “detection” antibodies are applied. These also bind the proteins, leaving them sandwiched between two antibodies (hence the name of the technique). 4) Next, a secondary antibody is added. This one is linked to an enzyme (represented by a black dot in this diagram). 5) In the last step, a chemical substrate is applied and the enzyme converts it to a product that can be measured. Often, the enzymatic conversion will result in a color, shown here in red. The more protein present in the sample, the redder solution becomes. By comparing the results to control reactions with known amounts of protein, scientists can determine the exact concentration of the protein in their starting sample.

Witnessing the birth of a new scientific field

by Heather Buschman on June 14, 2011 at 1:04 pm | 1 comment

Full Article

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 33^rd 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.

Read More

Crunching the Proteome

by Josh Baxt on June 2, 2011 at 3:13 pm | 0 Comments

Full Article

Sophisticated proteomics equipment can now determine virtually the entire protein complement of a cell.

Every day we gain a better understanding of how cells work. In the past 20 years, new tools to examine gene expression and function have illuminated many different mechanisms that guide all aspects of cellular behavior. However, to fully understand normal cellular functions and how they malfunction in disease, we need more in-depth information about the many proteins our genes produce. Which proteins are being produced? How are they modified? What is each protein’s ultimate function and how do they interact on a system-wide level? New technologies in the proteomics facility at Sanford-Burnham are providing reams of data that could help answer these and many other questions.In a room full of advanced technology, the Thermo LTQ-Orbitrap Velos mass spectrometer system stands apart. The system has been part of the proteomics toolbox for about a year and has proven its value identifying proteins several times over. Dr. Laurence Brill, director of Advanced Proteomics in Sanford-Burnham’s Proteomics Facility, notes that the Velos system is 10 times more sensitive and three times faster than previous machines, but there’s a lot more to the core’s success than the excellent equipment. “We use very stringently applied analytical methods that take years to develop and refine,” says Dr. Brill. “We are thinking very carefully about the goals and biology of each assay and making them reproducible from run to run.”

Systems Biology: anatomy of a network

by Communications Staff on May 13, 2011 at 6:00 am | 0 Comments

Full Article

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?”

On the road from stem cell to neuron

by Heather Buschman on May 5, 2011 at 10:29 am | 0 Comments

Full Article

During embryonic development, only neural crest stem cells expressing the SOX2 gene go on to become neurons. (Cartoon by Valeriya Yanushevskaya)

During embryonic development, only neural crest stem cells expressing the SOX2 gene go on to become neurons in the brain. (Cartoon by Valeriya Yanushevskaya)

Early in embryonic development, the neural crest – a transient group of stem cells – gives rise to parts of the nervous system and several other tissues. But what determines which cells become neurons and which become other cell types? It turns out a gene called SOX2acts as a stem cell gatekeeper – only cells expressing it have the potential to become neurons.The SOX2 gene encodes a transcription factor, a type of protein that switches other genes on or off. SOX2 is one of two key genes researchers use to generate induced pluripotent stem cells (iPSCs), which are capable of differentiating into all cell types for research and potential therapeutic applications.

In a paper published May 5 in the journal Cell Stem Cell, Drs. Alexey Terskikh, Flavio Cimadamore and colleagues show that SOX2 maintains the potential for neural crest stem cells to become neurons in the peripheral nervous system, where they interface with muscles and other organs. These results could help better inform therapies aimed at neurocristopathies, diseases caused by defects in the neural crest, which include microphthalmia and CHARGE syndrome.

According to Dr. Cimadamore, post-doctoral researcher and first author of the study, “Neural crest cells are notoriously difficult to study in humans because of their very early and transient nature – a woman is usually not even yet aware of her pregnancy when they start to migrate and differentiate. So here we took advantage of an embryonic stem cell-based model of human neural crest previously developed in our lab to get a better understanding of the molecular pathways that control the differentiation potential of such cells in humans.”

Doing the Math

by Heather Buschman on April 26, 2011 at 9:03 am | 0 Comments

Full Article

Cryobiologist Dr. Igor Katkov, standing next to a cryo tank where billions of cells are preserved.

Dr. Igor Katkov is a cryobiologist. (No, he isn’t trying to freeze human beings for future revival – that’s the pseudoscience cryonics, which Dr. Katkov and the overwhelming majority of his colleagues consider fraudulent.) He studies the effects of low temperatures on living things. More specifically, Dr. Katkov tries to find better ways to freeze cells for storage. This is especially important in our Stem Cell Research Center, where special stem cell lines must be carefully preserved. This is a lot harder than you might think.

“There are five main cellular factors to achieve optimal freezing,” Dr. Katkov explains. “These are the size of the cell, the surface area, the permeability of the membranes to water and solutes and the osmotically inactive volume of the cell (the non-water part of the cell).”

Top Stories - Basic Research

Florida Department of Health and Sanford-Burnham to kick off collaborative research program

Drug discovery case study: high-throughput screening of TNAP

A “twisted” grand opening ceremony

Why the economy depends on federal funding for medical research

International Proteolysis Society “cuts it up” in San Diego

Autophagy 101

Shared resources, shared successes

Taste receptors…in the gut?

Science…under the Tuscan sun

Happy Birthday ELISA

Witnessing the birth of a new scientific field

Crunching the Proteome

Systems Biology: anatomy of a network

On the road from stem cell to neuron

Doing the Math

Search

About Beaker

Support us

Categories

@SanfordBurnham’s tweets

Top Stories - Basic Research

Search

About Beaker

Support us

Categories

@SanfordBurnham’s tweets

Search by Keyword