And The Winners Are

Jan. 3, 2014

By Medical Discovery News

The Nobel Prize

Inside each living cell is a complex system of roadways, each used to transport molecules so the cell can keep performing the processes it was made to do. Like highways that span from one state to another, cells can even use the roadways to deliver molecules to other cells. How cells are able to do this has been an intense area of study for years, and thanks to three Nobel prize-winning scientists, it’s a little more understood now.

This year’s Nobel Prize for Physiology or Medicine was awarded to scientists who have unraveled the mysteries of how cells route or traffic specific molecules to the correct locations.  The $1.4 million prize was split between Drs. James Rothman of Yale University, Randy Schekman of University of California-Berkeley, and Thomas Sudhof of Stanford University. Their work revealed a basic element of cell physiology that is essentially the same for all cells, from single-celled yeasts to complex mammals like humans.

The basic mode of transporting molecules in cells is in a vesicle – hollow, spherical structures that carry molecules inside. Molecules are packaged at different places in cells and then safely transported at the right time to the correct destination via vesicles. But how does this transportation container know where to drop off its delivery? With mail, a zip code is written on the outside of a letter specifying a precise location where it is to be delivered. With vesicles, there are specific proteins on the outside surface of the sphere that specify where its cargo is to be delivered, whether it’s within a cell or to the cell’s surface, to be released from the cell to other cells. With the right cellular zip code, molecules are delivered to the right place.

Schekman discovered the genes and proteins that regulate these vesicles. They are the traffic cops that control vesicle traffic through the cells. He found that different genes and proteins determined whether a vesicle delivered its contents to the cell’s surface or to different compartments inside a cell. While he studied this in yeast cells, similar genes and proteins have been found in more complex animals such as mice and humans.

Rothman found the specific proteins on the surfaces of vesicles that represent molecular zip codes and allow the vesicles to interact with proteins at their correct destinations. The interaction between these two groups of complementary proteins causes the vesicle to fuse with the membrane at its intended destination and release its contents.

Sudhof revealed how nerve cells communicate with each other and how calcium ions control this activity. He found that calcium ions act as a trigger, causing vesicles to fuse with cell surfaces and release the molecules to interact with neighboring cells, transmitting signals along a nerve.

This transportation system is used for critical functions in humans, like brain signals and immune responses, so problems within the system can cause disease. These pioneers have provided an incredible understanding upon which others can continue to build.

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The Human Genome Revisited

March 1, 2013

By Medical Discovery News

When scientists sequenced the human genome in 2000, it revolutionized biomedical research, much like the invention of the Internet forever changed communications. The project aimed to identify all the genes in the human genome.

At first, they estimated that humans had less than 100,000 genes, then improved methods lowered that to 35,000, and a new analysis suggests that humans have no more than 21,000 genes. When considering the complexity of a human being, that number does not seem very high.

However, even the highest of those estimates accounted for less than 20 percent of the DNA sequence in the human genome. The rest of sequence did not appear to encode genes that led to proteins and was therefore considered non-functional or “junk” DNA.

Now a recent study by more than 400 researchers at 32 institutions costing almost $300 million challenges that notion and suggests that more than 80 percent of the human genome is indeed utilized and therefore important in the overall biology of each person – so much for “junk” DNA. The Encyclopedia of DNA Elements (ENCODE) project concluded that 20,687 genes produce proteins and an additional 18,400 genes produce RNA involved in coordinating the activity of the genes that produce proteins. 

This extensive effort originally focused on the genomes of a small number of human cells but later expanded to include almost 150 different cells, including immune, embryonic, liver tissue, umbilical cord, and cancer cells. Specific genes produce proteins for different tissues at different stages of human growth, so using this wide array insured that the analysis included all active genomic regions and gave a broader view of the genome. 

The analysis also identified genome regions associated with specific human diseases, creating an opportunity for better understanding these diseases and treating them. In addition, the ENCODE project revealed just how different humans are from other mammals like monkeys, dogs, or dolphins. While previous estimates suggested that just 5 percent of the human genome is unique from other animals, ENCODE’s research doubled that estimate to almost 10 percent. Another revelation showed just how complex the control mechanisms of the human genome really are. They signal almost 20,000 genes at the exact time and location to allow a fetus to develop normally and instruct the specific workings of tissues, like in the kidneys, lungs, or brain.

So the action of genes is controlled by layer upon layer of interacting and intricate controls that make each person who they are. Homo sapiens are a species of biological wonder and will require many years of intense study to even begin to understand the mysteries of how genes are regulated to make a human being. 

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