Lecture 2 - Cell Biology PDF

Introduction to Behavioral Neuroscience PSYC 211 Lecture 2 of 24 – Cell Biology (Chapter 5-1; pp137-149) Professor Jonathan Britt Questions? Concerns? Please write to [email protected] 1  WHAT IS STUFF MADE OF? All ordinary matter in...

Introduction to Behavioral Neuroscience PSYC 211 Lecture 2 of 24 – Cell Biology (Chapter 5-1; pp137-149) Professor Jonathan Britt Questions? Concerns? Please write to [email protected] 1  WHAT IS STUFF MADE OF? All ordinary matter in the universe is made of atoms. Atoms are made of protons, neutrons, and electrons. The formation of these atoms releases light (mostly red to infrared light with a wavelength around 0.001 mm) Light from the formation of the first atoms has been traveling through space for 13.7 billion years. The ongoing expansion of the universe has caused these wavelengths of light to stretch 1000-fold. (wavelength ~1 mm) We cannot see this light with our eyes, but we can detect it all around us. We call it cosmic microwave background radiation. >99% of the atoms in the universe, just like in our sun, are hydrogen and helium. These atoms formed 380,000 years after the big bang (13.7 billion years ago), when the universe had cooled enough for electrons to stably associate with protons and neutrons. 2 THE TIMELINE OF OUR UNIVERSE Earth, Formation today of Earth 3  THE TIMELINE OF OUR UNIVERSE A light year refers to a distance, the distance light travels in one year. 46 billion light years Every day, light from the creation of the first atoms Earth, hits our planet today (from all directions) This light has been traveling for 13.7 billion years. The areas of space where this light originated are now further away from our planet than they used to be, due to the continued expansion of the universe. These locations are now 46 billion light years away from us, and they continue to move away from us (much faster than the speed of light). 4  ORDINARY MATTER The atoms on the periodic table are the most basic chemical elements. They cannot be broken down into other substances by a normal chemical reaction. Atoms are identified by their atomic number (the number of protons in the nucleus). The air we breathe is largely (99%) N2 and O2. 118 elements have been identified, but only the first 94 occur naturally on Earth. 5  WHAT ARE MOLECULES? Atoms interact with each other when it improves their ability to balance out or distribute their electrical charges. The sharing of electrons creates a covalent bond. A molecule is two or more atoms connected with covalent bonds (e.g., the water molecule H20). One property of covalent bonds is that they do not break apart in water. When a molecule is created, broken apart, or modified, it is a chemical reaction. Chemical reactions can just involve a change in the position of electrons in the molecule. Chemical reactions change how molecules interact with other molecules. The likelihood of a chemical reaction depends on many factors, like temperature. Living entities (cells) regulate chemical reactions to grow and manipulate their environment. 6  WHAT ARE SALTS? Atoms interact with each other when it improves their ability to balance out or distribute their electrical charges. When an atom or molecule has a net electrical charge (positive or negative), we call it an ion. Negatively charged ions can donate an electron to positively charged ions, creating an ionic bond. Atoms and molecules connected with ionic bonds are called salts (e.g., table salt, NaCl, sodium chloride). Salts dissolve in water because ionic bonds break apart in water. dry table salt (NaCl) table salt in water (H2O) ions + - ionic bond Water molecules neutralize excess electrical charges better than ionic bonds do. 7  EVOLUTION Planet Earth formed 4.5 billion years ago Sometime in the first billion years, one self-replicating cellular entity emerged out of the “primordial soup” 8  THE ATOMIC COMPOSITION OF CELLS The atoms found in cells are: 59% Hydrogen – H – an atom with 1 proton 24% Oxygen – O – an atom with 8 protons 11% Carbon – C – an atom with 6 protons 4% Nitrogen – N – an atom with 7 protons 2% Others (phosphorus, sulfur, …) CHNOPS CHNOPS stands for carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. These atoms represent the six key chemical elements whose covalent combinations make up most of the biological molecules on Earth. 9 THE ATOMIC COMPOSITION OF CELLS 10  THE MOLECULES OF LIFE The CHNOPS elements come together in different combinations to form the five main molecules that we find in cells: 1) Water 2) Sugar 3) Fat (Lipid) 4) Nucleotide 5) Amino acid These molecules, on their own, are considered to be small molecules. These molecules all formed naturally on Earth prior to the first lifeform. They have also all been found on asteroids that landed on Earth. Almost everything found in a cell is one of these molecules or it is made up of a chain of these molecules (e.g., a chain of interconnected sugar molecules). 11  THE CHAIN-LINK STRUCTURE OF THE MOLECULES OF LIFE Chains of small molecules are called macro-molecules (big molecules). 12  THE MOLECULAR COMPOSITION OF CELLS Beside water (70% of total cell mass), cells are made up of: 15% Sugar (chains of sugar molecules are called carbohydrates) 10% Fat (lipid molecules congregate to form cell membranes and vesicles) 15% Nucleotides (nucleotides chain together to form nucleic acids; RNA and DNA are types of nucleic acids). 50% Amino acids (long chains of amino acids are called proteins; short chains of amino acids are called peptides) 10% Other organic molecules made of the CHNOPS atoms as well as salts (e.g., table salt: NaCl) 13  THE BEGINNING OF LIFE RNA is a type of nucleic acid, specifically a ribonucleic acid. Strands of RNA can naturally fold into complex 3-dimensional shapes, and some of them can catalyze chemical reactions – the key to life. RNA molecules that can catalyze chemical reactions are called ribozymes. Life probably started where ribozymes naturally formed, since they can spontaneously 1) interlink nucleotides to form nucleic acids (RNA and DNA) 2) interlink amino acids to form proteins These three types of molecules (RNA, DNA, & proteins) play a central role in all cells on planet Earth. Depictions of ribozymes 14  FROM RIBOZYMES TO CELL BIOLOGY Ribozymes may have been central to the start of life, but they no longer play a big role. There are two main problems with ribozymes, which are molecules of RNA. 1) RNA is fragile. It breaks apart easily. 2) RNA is made of 4 different types nucleotides that are not particularly abundant on planet Earth. It would have been severely limiting/impractical for cells to rely on ribozymes to regulate the chemical reactions they need to grow and divide. There is a greater abundance of amino acids and a greater diversity of them (>20 different types). These amino acids can be strung together in different combinations to form proteins of all different shapes and sizes. Proteins that catalyze chemical reactions are called enzymes. Enzymes quickly became the main catalyst of life’s chemical reactions. Cells evolved a way to make proteins in a highly consistent and well-regulated manner. They used the strands of RNA floating around as instructions for how to put amino acids together (in what order) to form useful proteins. 15  PROTEINS Proteins are what do things in a cell. They are the enzymes that catalyze chemical reactions. They are the receptors that sense the world around us. They make up the scaffolding and roads within a cell. They mediate transport and storage and serve as messengers. Proteins are chains of amino acids. They are between 100 and 1000 amino acids long (containing between 2,000 to >100,000 atoms). They are considered macromolecules (big molecules). The smallest things our eyes can see unaided are 0.1 mm long. Proteins are about 0.000003 mm long. 16  PROTEIN SYNTHESIS Cells need two types of RNA (and a bunch of free amino acids) to synthesize a protein: 1) a long, unfolded strand of RNA, called mRNA, which represents the instructions. 2) a bunch of short, folded up pieces of RNA, called tRNA, which read the instructions. tRNA molecules are about 76 nucleotides long (around 4000 atoms). On one end, there are 3 exposed nucleotides that can bind a complementary 3-nucleotide sequence of mRNA. On the other side, there is pocket that is highly attractive to a free-floating amino acid. There are 20 types of amino acids, and there are unique tRNA molecules to carry each of them. Cells make proteins by encouraging tRNA molecules to find a sequence of mRNA that they complement. Then, a chemical reaction is needed to interlink the amino acids that are held by the tRNA molecules. Based on the sequence of the genetic code, 20 types of amino acids get strung together in different combinations to form all the proteins of life. amino acid free-floating tRNA strand of mRNA molecule 17  RIBOSOME – THE FIRST ORGANELLE A ribosome is a molecular machine that is made of RNA and proteins (> 300,000 atoms in total). Ribosomes have perfected the synthesis of new proteins by stringing together the amino acids held by tRNA molecules in the order determined by free-floating strands of mRNA. How it generally works: The small subunit of the ribosome grabs a free-floating strand of mRNA. Then the large subunit of the ribosome identifies free floating tRNA molecules that complement the section of mRNA held by the small subunit. Ribosomes slide across mRNA, taking one step each time they find a tRNA molecule that complements the mRNA segment held by the small subunit. When a ribosome finds an appropriate (complementary) tRNA molecule, it removes its amino acid and attaches it to the amino acid of the next complementary tRNA molecule. Step by step, the ribosome links together amino acids held by tRNA molecules based on the sequence of nucleotides in free-floating strands of mRNA. Ribosomes synthesize new proteins by translating strands of mRNA, interlinking the amino acids held by tRNA molecules in the order determined by the genetic code. 18  WHY IS DNA SO IMPORTANT? Ribosomes are amazing at synthesizing proteins (by translating strands of mRNA). The problem is that RNA is not stable. It breaks apart too easily to be useful for long term information storage. DNA is much more stable and durable than RNA. DNA and RNA are complementary, so it is easy to transcribe one into the other. For long term information storage, cells evolved to use DNA instead of RNA. In general, for the last 3½ billions years on planet Earth: All the instructions of life are stored in strands of DNA. Sections of DNA are transcribed into mRNA. mRNA is translated into proteins (i.e., chains of amino acids). Protein enzymes catalyze the chemical reactions of life. 19  THE CELL MEMBRANE Phospholipids are strands of fat (lipids) with a phosphate cap. Lipids prefer the company of other lipids. Phosphate caps prefer to interact with water. Phospholipids form bilayer sheets if left undisturbed (in water). When shaken, phospholipids form micelles (soap bubbles). Under the right conditions, micelles can pop and reform as liposomes. The cell membrane is basically a liposome. Diffusion through the phospholipid bilayer is limited. Inside and outside are salt water. 20  THE PROKARYOTIC CELL (BACTERIA & ARCHAEA) cell membrane Ribosomes floating in cytoplasm DNA The first cells were prokaryotic cells, which consist of a cell membrane filled with cytoplasm. Cytoplasm is basically saltwater filled with sugar, nucleic acids, and amino acids. Floating within the cytoplasm of prokaryotic cells are … 1) Loose strands of DNA and RNA (i.e., chains of nucleotides) and 2) Ribosomes: organelles made of RNA and proteins. Ribosomes interlink amino acids in the order dictated by the genetic code. Ribosomes synthesize proteins by translating the RNA that was transcribed from DNA. 21  EVOLUTION Planet Earth formed 4.5 billion years ago Within the first billion years, a simple prokaryotic cell formed Sometime in next 2 billion years, complex eukaryotic cells evolved 22  THE EUKARYOTIC CELL Eukaryotic cells are similar to prokaryotic cells, but they have… 1) mitochondria: molecular machines that extract energy from nutrients. Mitochondria generate molecules of ATP by digesting molecules of sugar. and 2) a nucleus, which safely imprisons the cell’s DNA. A chromosome is a compacted strand of DNA in a nucleus. Chromosomes are not allowed to leave the nucleus. 23  DNA & PROTEIN SYNTHESIS The genome of a cell refers to its entire collection of DNA. The genome provides the information necessary to synthesize all the cell’s proteins. Sections of the genome that get transcribed into RNA and translated into protein are called genes. A gene is a section of DNA that codes for a specific protein. When a gene is read, that segment of DNA is transcribed into RNA in the nucleus. RNA is allowed to leave the nucleus, so it can meet up with a ribosome to be translated into a protein. Humans have nearly 20,000 (protein-encoding) genes in their genome. These genes make up less than 2% of the human genome. Large sections of our genome (~20%) are never transcribed into RNA. Other sections (~78%) are sometimes transcribed into RNA, but this RNA does not code for proteins. Non-protein encoding strands of RNA seem to mostly regulate gene expression. In multicellular organisms, very few genes in the genome are expressed by all cells all the time. Most genes are only expressed by some cells some of the time. Gene expression varies cell by cell and is extremely well regulated by environmental cues. 24 See this video for a brief overview of protein synthesis.  THE EUKARYOTIC CELL BODY (SOMA) The cell body (or soma) of a cell is where its nucleus is located. Neurons are typically defined by where their soma is located (e.g., a hippocampal neuron). The cell membrane defines the boundary of Cytoplasm is water the cell. It consists of a filled with salt, sugar, phospholipid bilayer nucleic acids and that is embedded with amino acids. proteins. Microtubules allow for rapid transport of material within the neuron. See this cool video. Mitochondria are semi-autonomous double membrane-bound organelles. They are known as the powerhouse of the cell because they generate ATP, the cell’s main source of chemical energy. 25  EVOLUTION animals with nervous systems There are dozens of instances throughout history where collections of cells stuck together to form multicellular organisms. Once multicellular organisms evolved, the structure and function of life became almost limitless. Organisms known as animals first appeared around 650 million years ago. Nerve cells evolved shortly after that (~600 million years ago). 26  MULTICELLULAR ORGANISMS Multicellular organisms consist of more than one cell. In multicellular organisms, cells specialize to perform distinct functions. All cells within a multicellular organism have the same genome (the same collection of DNA), but they read different parts of it. For example, brain cells express different genes (read different parts of the genome) than heart cells do, even when these cells are part of the same animal (and thus have the same genome). It is the unique gene expression patterns between the different cells in a multicellular organism that give each cell its unique identity and function. Although prokaryotic cells sometimes form multicellular clusters, all complex multicellular organisms are exclusively eukaryotic. 27  HOW WE STUDY THE BRAIN Because of ethical considerations, most people around the world now strongly object to the use of ANY humans for invasive studies of brain function (unless there nearly no chance of harm). Given that cultural edict, what person do you think advanced the field of neuroscience the most? Charles Darwin The theory of evolution suggested that we could learn a lot about the human brain by studying the brains of other animals, and people around the world still find it somewhat acceptable to conduct invasive brain research on some animals. All animals (all cells) have a lot in common, because they all descended from a common ancestor – the very first cell. 28  HOW DO NEURONS WORK? Nerve cells haven’t changed much in the last 200 hundred million years. So, to understand how human neurons work, you can study a squid. The 1963 Nobel Prize was awarded for describing how (squid) neurons transmit electrical signals (i.e., the action potential). 29  HOW DOES LEARNING AND MEMORY WORK? The 2000 Nobel Prize was awarded for describing the neuronal basis of learning and memory. This work was done in a sea slug. But obviously, we can learn more about the human brain by studying the brains of animals that are evolutionarily more similar to us. 30  CHIMPS KIND OF LOOK AND ACT LIKE US Many societies have now outlawed invasive research involving the great apes, our closest living relatives. The great apes alive today (besides us) include chimpanzees, gorillas, orangutans, and bonobos. The human genome is very similar to the genomes of the other great apes. Humans and chimpanzees share 98.8% of their DNA. Keep in mind that humans have much bigger brains (> 3x) and way more neurons than any other great ape. Across species, neuron number generally correlates with cognitive complexity, but some whales, dolphins, and elephants have bigger and heavier brains than humans, and they do not seem to have our cognitive complexity. 31  OTHER TYPES OF MAMMALS Of the mammalian species alive today, 40% are rodents and 20% are bats. Rodents are evolutionarily closer to humans than most other mammalians species, including bats, cats, dogs, horses, dear, goats, pigs, cows, bears, elephants, raccoons, dolphins, etc. Because of the genetic and behavioural similarities between rodents and humans, as well as their small size, rodents have become the dominant species used in neuroscience research. bats 32  MAMMALIAN BRAIN STRUCTURE Although brain size (and neuron number) varies massively between mammalian species, brain structure is highly similar. Human brain Mouse brain 33  HOW ARE RODENTS LIKE US? Rodents are like us in many ways. They have complex decision-making abilities. They also get stressed out, depressed, and anxious. Human brain By learning how the brains of rodents generate hunger, sexual arousal, sleep, and aggression, we get a good idea of how similar processes work in humans. We use rodents to study the neural mechanisms of sensory, motor, and cognitive processes, including motivations, emotions, learning and memory, and decision-making. We model human diseases in rodents, giving Mouse them chronic pain, cancer, emotional brain disturbances, etc., to figure out how best to treat these conditions in humans. In 1865, Claude Bernard wrote that “the science of life is a superb and dazzlingly lighted hall which may be reached only by passing through a long and ghastly kitchen.” 34  HUMAN BRAINS ARE UNIQUE IN MANY WAYS Human brains develop very slowly (over the course of 20 years). This prolongation of maturation is referred to as neoteny (extended youth), and it is especially dramatic in the human species. Our slow maturation time sets us apart from other great apes and other animals with large brains. Our brains and our behaviour remain plastic (malleable, shapeable) far longer than other animals. At birth, the average human brain weighs 350 grams. Twenty years later, it weighs close to 1400 grams—four times weight of a newborn's brain. This growth is not due to the birth of new neurons; the human brain largely stops making new neurons halfway through its gestation in the womb. This growth is attributed to the growth of existing neurons, which continue to establish new connections with other neurons throughout life. It also reflects increases in the number of other cells in the brain (the support staff), which continue to replicate throughout the lifespan. 35  HOW LUCKY ARE WE TO BE ALIVE? Given the properties of planet Earth, how likely was the formation of life and the evolution of intelligent, verbal beings? Was this development inevitable given the billions of years or was it highly improbable? Were we just lucky? 36  WHERE IS EVERYBODY? THE FERMI PARADOX Within our local area of space (the Milky Way galaxy) there is estimated to be 40 billion earth-like planets that could support life. The Milky Way galaxy is over 13 billion years old, so some of its earth-like planets are likely way older than planet Earth (which formed 4.5 billion years ago). If interstellar travel is possible, even the "slow" kind that is nearly within our reach, we estimate a lifeform could colonize the entire Milky Way galaxy in less than 50 million years. Outside of the Milky Way, the observable universe contains over 2 trillion other galaxies. Many of these galaxies are much bigger than the Milky Way. It is hard to fathom how many earth-like planets could be out there. So…why haven’t we seen any aliens? Where is everybody? Could it really be just us? 37