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Investors - Biochemistry 101 Tutorial for ARYC Investors to Explain the Scientific Underpinnings of Arrayit Technology
Arrayit offers a brief educational tutorial on the scientific field of biochemistry to help our investors better understand our company. Let’s begin with the word “biochemistry”. Biochemistry is a two-part word derived from “bios” meaning “life” in Greek, and “chemie” meaning “chemistry” in German. Biochemistry is therefore the study of the chemistry of life, and a scientist who practices biochemistry is called a biochemist. Arrayit President and Chief Science Officer, Dr. Schena, is a professional biochemist, and Arrayit Corporation is a world leader in providing biochemistry tools for scientists and doctors.
What does it mean to study the chemistry of life? Biochemistry attempts to understand human beings and other life forms by studying the molecules found inside living cells. We begin our journey into the field of biochemistry by learning about the sizes and numbers of cells and molecules in field of biochemistry.
Cells and molecules
Take a moment and look closely at a human hair. A human hair is 100 microns wide, about the same width as a sheet of paper. At 100 microns in width, a human hair is very thin but is still visible to human eye. The size of a typical human cell is about 50 microns wide, or about half the width of a human hair. The human body is composed of a huge number of cells. There are approximately 10 trillion or 10,000,000,000,000 cells in the human body. If a human cell were the size of a beach ball, the cells in the human body would cover the entire land mass of the United States. The human body contains different types of cells such as skin cells, liver cells and brain cells. Every cell in the human body contains DNA and protein molecules, the molecules of life. Human blood cells are very helpful in biochemistry because blood cells contain the molecules of life, and blood cells are easy to obtain from patients simply by asking for a few drops of blood.
Now let’s take a journey inside the cell and investigate the structures and molecules in cells. The round compartment inside the cell is called a nucleus. The nucleus is important in biochemistry because the nucleus contains the DNA. A typical nucleus is about 5 microns wide, or about 20 times smaller than a human hair. The DNA molecule in the nucleus is very, very small, measuring about 0.002 microns in width, or about 50,000 times smaller than a human hair. Protein molecules present in cells are somewhat larger than DNA molecules, but are still very, very small. A typical human protein is about 0.01 microns wide or about 10,000 times smaller than a human hair. DNA and protein molecules are so small that they are invisible to the naked eye and to all but the most powerful laboratory microscopes. Nonetheless, DNA and protein carry out the biochemical functions essential for life and Arrayit has sophisticated tools for deciphering DNA and protein.
Almost everyone has heard of DNA by watching high profile cases on television. DNA stands for deoxyribonucleic acid. DNA is the genetic blueprint. It contains all of the genetic information required for life. DNA molecules are composed of four biochemical letters: A, G, C and T. The biochemical letters of DNA are connected in a sequence to form genes. A 15 letter portion of the human gene known as beta globin is shown here, along with the 15 letter beta globin sequence from a person with sickle cell anemia.
beta globin gene: GTTGGTGGTGAGGCC
sickle cell gene: GTTGGTGGTAAGGCC
Notice that the two gene sequences are identical except for a single letter variation in the beta globin sequence from the person with sickle cell anemia. The sickle cell patient has an “A” letter instead of a “G” letter in their DNA sequence. Variations in DNA sequences can cause human disease. Arrayit technology allows the very rapid identification of disease-causing variations in patient DNA.
The DNA molecule is long and thin and contains two chemical strands like the two rails of a railroad track. A protein in the cell called DNA polymerase acts like a locomotive and travels down the DNA “railroad track”, making a copy of the DNA as it goes. As the human body develops, cells divide to make more cells and the DNA is duplicated every time a cell divides. Because the DNA sequence is so complex, mistakes are sometimes made when the DNA is copied by polymerase. These mistakes or variations in the DNA are known as SNPs (pronounced “snips”). SNPs are passed on from generation to generation. Most SNPs occur between genes, and ride along silently in the genome. But when a SNP occurs in a gene, the results can be serious. As we saw above with the beta globin gene, a single letter variation in the DNA code can cause a disease. Given the importance of human disease, identifying and studying variations in the DNA sequence is a key activity in biochemistry.
The complete DNA blueprint in humans (the human genome) contains a total of 3 billion letters. The 3,000,000,000 A, G, C and T letters are connected together to form the genes and chromosomes. The human genome contains about 25,000 genes distributed across 24 chromosomes. Human genes vary greatly in length from a few thousand to a few million letters. The 24 chromosomes are tightly wound like a ball of yarn so that they fit inside the nucleus of each cell in the body.
Chemical bonds between the A, G, C and T chemicals on the two DNA strands hold the DNA strands together. Using the railroad track analogy, if the two DNA strands are the rails of the track, the chemical bonds between the A, G, C and T letters would be the railroad ties. Velcro is also a good analogy for DNA because, like velcro, the DNA strands are held tightly together but they can be separated by force. A biochemist can apply chemical force to DNA by raising the temperature. If the temperature of the DNA is raised to boiling (100C or 212F), the two DNA strands fall apart. If the temperature is reduced, the two DNA strands quickly reconnect like a zipper. A biochemist can make good use of the zipper-like quality of DNA. By placing one strand of the DNA “zipper” on a glass slide, the glass slide can be used to examine the other strand of DNA from a human patient. A powerful biochemistry tool known as a microarray contains “DNA zippers” from all 25,000 human genes. Microarrays allow scientists and doctors to examine every gene in the human body in a few hours. Because gene malfunctions can cause disease, microarrays have become very widely tools used in medical research. Arrayit Corporation is a world leader in microarray technology. To date, Arrayit customers have used Arrayit products to manufacture an estimated 100 million microarrays.
Proteins are the molecules inside cells that carry out the genetic instructions of the DNA blueprint. Each of the 25,000 genes in the human body produces a unique protein molecule, so there are 25,000 different proteins in the human body. One special class of proteins are known as enzymes. As discussed above, the protein in the cell that copies the DNA is known as DNA polymerase. DNA polymerase is a very important enzyme in the cell. Proteins are made of biochemical letters known as amino acids. There are 20 amino acid letters in the protein code. Amino acids are linked together like beads on a necklace to form proteins. A typical protein in the human body contains about 600 amino acids. Amino acids are required in the human diet because cells need to use them to make protein molecules.
A five amino acid portion of the human beta globin protein is shown here, along with the beta globin protein from a person with sickle cell anemia. The five amino acids shown here are produced in the cell from the 15 letter beta globin DNA sequence shown above.
beta globin protein: Val-Gly-Gly-Glu-Ala
sickle cell protein: Val-Gly-Gly-Lys-Ala
Notice that the two protein sequences are identical except for a single amino acid variation in the sickle cell protein. The sickle cell patient has an “Lys” letter instead of a “Glu” letter in their beta globin sequence. Lys stands for the amino acid lysine and Glu stands for the amino acid glutamatic acid. Sickle cell patients have a lysine amino acid instead of a glutamamic acid amino acid because of the single letter variation in the beta globin gene sequence. Variations in the DNA cause human disease because DNA variations result in variations in protein sequence as illustrated here. The beta globin protein normally works to transport oxygen from the lungs to other organs and muscles of the human body. The sickle cell protein does not transport oxygen very efficiently and sickle cell patients have anemia resulting from oxygen deficiency.
The 25,000 different protein molecules in the cell are found in many different shapes and sizes, like pieces of an elaborate biochemical puzzle. The puzzle analogy for proteins is a good one because, like pieces of puzzle, protein molecules connect with each other in a very specific way. Only certain proteins connect with each other, and these specific interactions are very important for the proper workings of the cell. Some types of sickle cell anemia are caused because the beta globin proteins cannot connect to each other properly. Biochemists spend a lot of time investigating how proteins in the cell connect to one another because protein connections play an important role in human disease.
Protein molecules connect with each other chemical forces between amino acids on the protein surface. One particularly strong type of interaction occurs between a special class of protein molecules known as antibodies. A biochemist can use antibodies to measure the proteins in the human body. The antibodies are attached to a glass slide to make an antibody microarray. The antibody “puzzle pieces” are then mixed with a protein sample from a patient, which contains protein “puzzle pieces”. The antibody and protein puzzle pieces connect to each other on the microarray and this allows scientists and doctors to measure the proteins present in the human body, such as in the bloodstream. Serious illnesses such as ovarian cancer and prostate cancer produce unusual proteins in the blood. Arrayit is using antibody microarrays to measure blood proteins as a way to detect disease at an early stage. Early stage disease detection is important because it makes illnesses such as cancer much easier to treat. Arrayit is a world leader in providing antibody microarrays to scientists and doctors for disease detection.
Symphony of life
The human body contains an elaborate and magical network of genes and proteins that work together to carry out the symphony of life. We use a symphony orchestra as a way to think about the human body because the genes and proteins in cells act like members of an orchestra, performing specific biochemical tasks to keep the body working properly. As we saw in the case of the beta globin gene, just one variation in the 3,000,000,000 letter DNA code can cause sickle cell anemia. The same is true for thousands of other human diseases. Understanding variation in DNA and protein sequences is a major focus for Arrayit. Arrayit uses microarrays as powerful devices for detecting gene and protein variants, and is a world leader in these areas.
We have discussed the fact that DNA is the genetic blueprint and that the DNA blueprint is present in every cell in the human body. The DNA blueprint is inherited from our parents and is passed down through the generations. Polymerase sometimes uses the wrong letter when copying the DNA, and this introduces sequence variants into the blueprint. Polymerase is a highly accurate enzyme, so all human beings have blueprints that are more than 99.9% identical to each other. But the human genome is so large (3,000,000,000 letters), 99.9% identity means that there are on average about one million sequence variants between any two people. Most of these sequence variants ride along “silently” in the blueprint because they occur in regions of the DNA between the genes on the chromosomes. Nonetheless, a significant number of sequence variants or SNPs occur within genes and cause changes in protein sequences. Some of these changes can impact important issues such as human health and longevity.
The DNA blueprint remains the same for the entire life of a person. The genetic code that we inherit from our parents is with us for our entire lives. The amount of DNA also remains the same. Each cell in the human body contains one genome located in the nucleus. The sequence of proteins also remains the same for our entire lives because the cell uses the DNA blueprint to make proteins. What is very different about proteins compared to genes is the amount of protein contained in cells. Some genes produce very large quantities of protein and some genes produce very small quantities of protein. Many genes also produce different quantities of protein depending on their location in the human body. Some proteins are produced at very high levels in the liver but at very low levels in the brain. Some proteins are produced in the blood stream but not in muscles. Proteins levels also change throughout our lives. Some proteins are only produced when we are babies, and other proteins are made late in life. Protein levels are affected by diet, medication, stress, gender, physical activity, and the weather.
The important and dynamic process that makes proteins from genes in the human body is known as gene expression. Gene expression, different from the DNA blueprint, changes throughout our lives depending factors ranging from the location in the human body where a protein is produced, to our age and health. Many human diseases are caused because proteins are produced at times or in locations where they should not be. Examining gene expression is a major activity in biochemistry, and microarrays are used in an estimated 100,000 laboratories all over the world to study and catalog gene expression. Arrayit President Dr. Mark Schena is a gene expression expert and Arrayit’s products and services are very widely used to measure gene expression. Many human drugs aim to fine tune gene expression so that the “music” created by cells sounds as nice as a symphony orchestra. Arrayit tools are used widely by drug companies to make safer and more effective medications.
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