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Curious Cat Science and Egineering blog full tag cloud
Related: How Bleach Kills Bacteria - Bacteria Survive On All Antibiotic Diet - Soil Could Shed Light on Antibiotic Resistance - Antibiotics Too Often Prescribed for Sinus Woes
Harvard researchers gain new insight into aging
Scientists have long known that aging causes gene expression to change, and DNA damage to accumulate. But now, research led by Harvard Medical School scientists explains the connection between the two processes in mammals.
The paper, published in the journal Cell, found that a multi-tasking protein called SIRT1 that normally acts as guardian of the genome gets dragged away to DNA fix-it jobs. When the protein abandons its normal post to work as a genetic handyman, order unravels elsewhere in the cell. Genes that are normally under its careful watch begin to flip on.
“What this paper actually implies is that aspects of aging may be reversible,” said David Sinclair, a Harvard Medical School biologist who led the research. “It sounds crazy, but in principle it should be possible to restore the youthful set of genes, the patterns that are on and off.”
The study is just the latest to draw yet more attention to sirtuins, proteins involved in the aging process
Aging is fascinating. By and large people just accept it. We see it happen to those all around us, without exception. But what causes biological aging? It is an interesting area of research.
Related: lobsters show no apparent signs of aging - Our Genome Changes as We Age - Millennials in our Lifetime? - Radical Life Extension - posts on cells
Developed more than 200 years ago and found in households around the world, chlorine bleach is among the most widely used disinfectants, yet scientists never have understood exactly how the familiar product kills bacteria. In fact, Hypochlorite, the active ingredient of household bleach, attacks essential bacterial proteins, ultimately killing the bugs.
“As so often happens in science, we did not set out to address this question,” said Jakob, an associate professor of molecular, cellular and developmental biology. “But when we stumbled on the answer midway through a different project, we were all very excited.”
Jakob and her team were studying a bacterial protein known as heat shock protein 33 (Hsp33), which is classified as a molecular chaperone. The main job of chaperones is to protect proteins from unfavorable interactions, a function that’s particularly important when cells are under conditions of stress, such as the high temperatures that result from fever.
“At high temperatures, proteins begin to lose their three-dimensional molecular structure and start to clump together and form large, insoluble aggregates, just like when you boil an egg,” said lead author Jeannette Winter, who was a postdoctoral fellow in Jakob’s lab. And like eggs, which once boiled never turn liquid again, aggregated proteins usually remain insoluble, and the stressed cells eventually die.
Jakob and her research team figured out that bleach and high temperatures have very similar effects on proteins. Just like heat, the hypochlorite in bleach causes proteins to lose their structure and form large aggregates.
These findings are not only important for understanding how bleach keeps our kitchen countertops sanitary, but they may lead to insights into how we fight off bacterial infections. Our own immune cells produce significant amounts of hypochlorite as a first line of defense to kill invading microorganisms. Unfortunately, hypochlorite damages not just bacterial cells, but ours as well. It is the uncontrolled production of hypochlorite acid that is thought to cause tissue damage at sites of chronic inflammation.
How did studying the protein Hsp33 lead to the bleach discovery? The researchers learned that hypochlorite, rather than damaging Hsp33 as it does most proteins, actually revs up the molecular chaperone. When bacteria encounter the disinfectant, Hsp33 jumps into action to protect bacterial proteins against bleach-induced aggregation.
“With Hsp33, bacteria have evolved a very clever system that directly senses the insult, responds to it and increases the bacteria’s resistance to bleach,” Jakob said.
Related: University of Michigan Press release - How do antibiotics kill bacteria? - NPR podcast on the story - Why ‘Licking Your Wounds’ Works - Researchers Learn What Sparks Plant Growth
The Nobel Prize in Chemistry 2008 is evenly shared by Osamu Shimomura, Boston University Medical School, USA; Martin Chalfie, Columbia University, New York, USA and Roger Y. Tsien, University of California, San Diego, USA for discovery and work with glowing green fluorescent protein.
The remarkable brightly glowing green fluorescent protein, GFP, was first observed in the beautiful jellyfish, Aequorea victoria in 1962. Since then, this protein has become one of the most important tools used in contemporary bioscience. With the aid of GFP, researchers have developed ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread.
Tens of thousands of different proteins reside in a living organism, controlling important chemical processes in minute detail. If this protein machinery malfunctions, illness and disease often follow. That is why it has been imperative for bioscience to map the role of different proteins in the body.
This year’s Nobel Prize in Chemistry rewards the initial discovery of GFP and a series of important developments which have led to its use as a tagging tool in bioscience. By using DNA technology, researchers can now connect GFP to other interesting, but otherwise invisible, proteins. This glowing marker allows them to watch the movements, positions and interactions of the tagged proteins.
Researchers can also follow the fate of various cells with the help of GFP: nerve cell damage during Alzheimer’s disease or how insulin-producing beta cells are created in the pancreas of a growing embryo. In one spectacular experiment, researchers succeeded in tagging different nerve cells in the brain of a mouse with a kaleidoscope of colors.
Osamu Shimomura, a Japanese citizen, was born 1928 in Kyoto, Japan. He received his Ph.D. in organic chemistry 1960 from Nagoya University, Japan. first isolated GFP from the jellyfish Aequorea victoria, which drifts with the currents off the west coast of North America. He discovered that this protein glowed bright green under ultraviolet light.
Martin Chalfie demonstrated the value of GFP as a luminous genetic tag for various biological phenomena. In one of his first experiments, he coloured six individual cells in the transparent roundworm Caenorhabditis elegans with the aid of GFP.
Roger Y. Tsien contributed to our general understanding of how GFP fluoresces. He also extended the colour palette beyond green allowing researchers to give various proteins and cells different colours. This enables scientists to follow several different biological processes at the same time.
Related: 2007 Nobel Prize in Chemistry - Nobel Laureate Initiates Symposia for Student Scientists - Nobel Prize in Chemistry (2006) - Webcasts by Chemistry and Physics Nobel Laureates
| Paul Rothemund, scientist at Cal Tech, provides a interesting look at DNA folding and DNA based algorithmic self-assembly. In the talk he shows the promise ahead for using biological building blocks using DNA origami — to create tiny machines that assemble themselves from a set of instructions.
Algorithmic Self-Assembly of DNA Sierpinski Triangles, PLoS paper. I posted a few months ago about how you can participate in the protein folding, with the Protein Folding Game. Related: Viruses and What is Life - DNA Seen Through the Eyes of a Coder - Synthesizing a Genome from Scratch - Evidence of Short DNA Segment Self Assembly - Scientists discover new class of RNA |
Synthetic molecules, derived from curcumin, a naturally occurring compound found in the spice turmeric have been killed cancer cells, in lab settings. Centuries of anecdotal evidence and recent scientific research suggest curcumin has multiple disease-fighting features, including anti-tumor properties. However, when eaten, curcumin is not absorbed well by the body. Instead, most ingested curcumin in food or supplement form remains in the gastrointestinal system and is eliminated before it is able to enter the bloodstream or tissues.
James Fuchs, assistant professor of medicinal chemistry and pharmacognosy at Ohio State University and principal investigator on the project, and colleagues are continuing to refine compounds that are best structured to interact with a few overactive proteins that are associated with cell activity in breast and prostate cancers. Blocking these molecular targets can initiate cell death or stop cell migration in the cancers.
A major component of their strategy is called structure-based, computer-aided design, a relatively new technology in the drug discovery field. Before ever working with an actual compound, the scientists can make manipulations to computer-designed molecules and observe simulated interactions between molecules and proteins to predict which structural changes will make the most sense to pursue.
“Most of the interaction between our compound and the overactive protein comes from what are called hot spots on the protein’s surface,” said Chenglong Li, assistant professor of medicinal chemistry and pharmacognosy at Ohio State and an expert in computational chemistry. “For each spot, we can design small chemical fragments and link them together to make a molecule. This is what computer-aided design and modeling can do.”
Some of the most effective compounds have been tested for their effectiveness against human cancer cell lines – as well as whether they might be toxic to healthy cells. So far, the molecule favored by the researchers has a nearly 100-fold difference in toxicity to cancer cells vs. healthy cells, meaning it takes 100 times more of the compound to kill a healthy cell than it does to kill a cancer cell.
Related: Full Press Release from Ohio State University - Cancer Killing Ideas From Honeybees - Cancer Deaths, Declining Trend - Cancer Cure, Not so Fast - Innovative Science and Engineering Higher Education
Using a light touch to measure protein bonds
With this technique, the researchers can get a precise measurement of the force holding the proteins together, which is on the order of piconewtons (10-12 newtons).
Related: Neuroengineers Use Light to Silence Overactive Neurons - Slowing Down Light - Foldit, the Protein Folding Game
New probe may help untangle cells’ signaling pathways
“We can use this to identify new protein partners or to characterize existing interactions. We can identify what signaling pathway the proteins are involved in and during which phase of the cell cycle the interaction occurs,” said Alice Ting, the Pfizer-Laubach Career Development Assistant Professor of Chemistry and senior author of a paper describing the probe published online June 27 by the Journal of the American Chemical Society.
The new technique allows researchers to tag proteins with probes that link together like puzzle pieces if the proteins interact inside a cell. The probes are derived from an enzyme and its peptide substrate. If the probe-linked proteins interact, the enzyme and substrate also interact, which can be easily detected.
To create the probes, the researchers used the enzyme biotin ligase and its target, a 12-amino-acid peptide.
Related: Specific Protein and RNA Labeling in Cells - Using Bacteria to Carry Nanoparticles Into Cells - Molecular Bioengineering and Dynamical Models of Cells - The Inner Life of a Cell (Animation)
Very cool animation, by Cold Spring Harbor Laboratory and Interactive Knowledge, of the working of the inner workings of our bodies as they react to a cut. If you want to get right to the science, skip the first minute. Providing these types of educational animations is a great way for educational institutions to take advantage of technology to achieve their mission in ways not possible before.
It is annoying how many of those “educational” institutions don’t provide such educational material online (and even take material offline that was online). Have they become more focused on thinking and operating the way they did in 1970 than promoting science education? It is a shame some “educational” institutions have instead become focused on looking backward. I will try to promote those organizations that are providing online science education.
Related: Inside Live Red Blood Cells - Universal Blood
Foldit is a revolutionary new computer game enabling you to contribute to important scientific research. This is another awesome combination of technology, distributed problem solving, science education…
Essentially the game works by allowing the person to make some decisions then the computer runs through some processes to determine the result of those decisions. It seems the human insight of what might work provides an advantage to computers trying to calculate solutions on their own. Then the results are compared to the other individuals working on the same protein folding problem and the efforts are ranked.
This level of interaction is very cool. SETI@home, Rosetta@home and the like are useful tools to tap the computing resources of millions on the internet. But the use of human expertise really makes fold.it special. And you can’t help but learn by playing. In addition, if you are successful you can gain some scientific credit for your participation in new discoveries.
Related: Expert Foldit Protein Folder, JSnyder - Researchers Launch Online Protein Folding Game - New Approach Builds Better Proteins Inside a Computer - Phun Physics - Protein Knots
The site includes some excellent educational material on proteins and related material. What is a protein:
Gator Blood May Be New Source of Antibiotics
For the study, the researchers extracted proteins known as peptides from white cells in alligator blood. As in humans, white cells are part of the alligator’s immune system. The researchers then exposed various types of bacteria to the protein extracts and watched to see what happened.
In laboratory tests, tiny amounts of these protein extracts killed a so-called “superbug” called methicillin-resistant Staphylococcus aureus, or MRSA. The bacteria has made headlines in recent years because of its killing power in hospitals and its spread among athletes and others outside of hospitals.
The extracts also killed six of eight strains of a fungus known as Candida albicans, which causes a condition known as thrush, and other diseases that can kill people with weakened immune systems.
Related: Entirely New Antibiotic Developed - Soil Could Shed Light on Antibiotic Resistance - articles on the Overuse of Antibiotics
The human genome is old news. Next stop: the human proteome
Related: $500m human map to trump DNA project - Human proteome project: 21000 genes/1 protein, 10 years, $1 billion? - Protein Knots - posts tagged: protein
The subtly different squid eye by PZ Myers:
Superficially, squid eyes resemble ours. Both are simple camera eyes with a lens that projects an image onto a retina, but the major details of these eyes evolved independently - the last common ancestor probably had little more than a patch of light sensitive cells with an opsin-based photopigment. The general properties of this ancient eye can still be seen in modern eyes. They detect light with a simple molecule called retinal that is capable of absorbing a photon, changing its shape from the 11-cis form to the all trans form; basically, it flips from a chain with a kink to a straight chain. Retinal is imbedded in a protein called opsin. When retinal changes shape, it changes the shape of the opsin protein, too, which can then interact with other proteins in the cell membrane.
The next protein in the sequence is called a G protein. G proteins are ubiquitous intermediates for many cellular processes; when a receptor, like opsin, is activated, it activates a G protein, which then activates other proteins, starting a signaling cascade. In the podcast, I compare this to starting an avalanche. Opsin is an agent standing on a hill; when it receives a light signal, it nudges a small boulder (the G protein), which then tumbles down setting a whole series of rocks in motion. The G protein is an intermediate which takes a small change, the initial nudge, and amplifies it into the activation of many other proteins.
Related: How the Human Brain Resolves Sight - Scientists Discover How Our Eyes Focus When We Read - 3-D Images of Eyes
Engineered Protein Shows Potential as a Strep Vaccine
Related: New and Old Ways to Make Flu Vaccines - MRSA Vaccine Shows Promise - New Approach Builds Better Proteins Inside a Computer
New Approach Builds Better Proteins Inside a Computer
A detailed understanding of a protein’s structure can offer scientists a wealth of information - revealing intricacies about the protein’s biological function and suggesting new ideas for drug design. Researchers often rely on x-ray crystallography to determine a protein’s structure - bombarding the molecule with x-rays and analyzing the resulting diffraction pattern to piece together its structure. But not all proteins are amenable to this time-consuming technique, and those that are do not always yield the atomic-level data researchers would like to have.
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The complex algorithms the researchers developed to carry out these analyses demand a tremendous amount of computing power. More than 150,000 home computer users around the world were an integral part of the project, volunteering their computers to participate in the quest for protein structures through Rosetta@home, a distributed computing project that is based on the Berkeley Open Infrastructure for Network Computing (BOINC) platform.
You can join in via Rosetta@home. Related: Protein Knots - molecular sieve advances protein research - Protein Science Art - Nobel Laureate Discusses Protein Power
As usually the latest issue of ScienceMatters@Berkeley includes several intersting articles including, The Protein Machine by Kathleen M. Wong
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