What is Life?

Biology is the study of life and living things. Since all living things are made up of atoms, chemistry is the first science that goes into understanding biology. I would recommend everyone learn about chemistry to build a foundation for biology.

The first thing we have to look at in biology is, what is a living thing? How do we classify what is alive and what isn't? We would all agree that a flower or a rabbit is alive while a stone or gold bar is not. Some things are not that easy. Is a virus really alive?

Cell Theory is the basic theory for biology. There are two principles to cell theory. The first is that all living things are made up of cells. The cell is the smallest unit of life. The second is that all life comes from cells. New life comes from existing cells. We know that a stone does not have cells so it is not alive. A tree is made up of cells so it is alive. When a new tree is made, it comes from the existing cells of the parent tree. This is done by creating seeds and pollen. Just as humans make eggs and sperm which are cells that carry the genetic information of the parents. They come together to create a cell containing the genetic information of both parents that grows into a whole new life.

All living things will have a few attributes that identify them as alive. Different courses will list these differently, but we will look at the key attributes of life. The first attribute is living things will reproduce. At one time, people believed life was spontaneously created, but now we know each cell will come from other cells. All cells have the ability to pass their genetic information to their offspring. The ability of a cell to copy and transmit its genetic information is a key attribute of living things.

All living things have the ability to grow and develop. They will develop through different stages of life. This requires them to take in some type of nutrition or energy that allows them to run cell processes. Even a simple bacteria needs to take in energy and resources to grow and divide from one cell into two. Plants take in sunlight, water and carbon dioxide while animals take in plants, water and oxygen to gain nutrients to grow and develop.

All living things need to expend energy to keep themselves in a good state of repair. The theory of entropy suggests that all things will tend toward a state of decay and disrepair. If you don't keep up your car or house, they break down and fall apart. In the same way, all living things take in energy and use it to keep themselves in good condition. Living things will try to regulate their internal systems to keep all things in balance. The human body has controls to balance out every system. The cells themselves will keep things in homeostasis.

All cells will also respond to external stimuli. Human cells have a system of signals and receptors that allow them to send and receive communications between them. One cell can also respond to the signals of another cell. Plant cells can respond to stimuli like sunlight. This can easily be seen by a plant that grows in the direction of sunlight. The plant cells can sense the light, and they grow toward it.

Living things will adapt and evolve to their environments. The genetics of living things tells us all living organisms will suffer mutations in their genetics. These mutations can be either good or bad. This is selected for or against by the environment of that organism. Adaptation and Evolution go together. The mutations which provide a survival or reproduction benefit will allow for more and better adapted offspring. Those that are bad mutations will be selected against. This is the concept of Natural Selection.

Now that we understand some of the key elements of life, we can see how some things, like a virus, could be controversial. It has no aspects of life when it's outside the cell, but when it's inside a cell, it takes on all the attributes of a living organism. Outside a cell, it can not reproduce, adapt, evolve, grow, or consume energy. Inside a cell, it does all these things.

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Cell Biology

The human body is made up of organs and each organ has a specific role in the larger organism. We have a heart to circulate blood, lungs to take in oxygen and stomach to digest food. In the same way the body has organs, the cells have organelles which are small parts of the cells with a specific function. Many if not all these organelles will be found in cells.

The Membrane is the first key structure of the cell. This is a lipid bilayer of phospholipids that surrounds the cell to keep the watery stuff inside separated from the watery stuff outside the cell. Nothing gets into or out of the cell unless it gets across the membrane. The membrane acts like a border between the inside of the cell and the outside environment. It has a host of receptors, adhesion molecules and channels that regulate everything that moves into and out of the cell.

The nucleus lies at the center of the cell. It contains all the genetic information of the cell that is used as a blueprint for everything the cell does. That makes the genetic information very important so it needs to be protected. The nucleus does this with another lipid membrane surrounding it. That allows the nucleus to regulate what can go into or out. There are sets of nuclear pores in the membrane that surround the nucleus that regulate traffic into and out of the nucleus.

The cytoplasm is the watery area between the cell membrane and the nucleus. You might think that this area would be like a bag of water, but it contains spider web-like structural proteins that give the cell its form. These structural proteins can also act like a network of roadways for transport proteins to move things around inside the cytoplasm. The majority of the work that gets done in a cell happens in the cytoplasm.

The endoplasmic reticulum is a structure that sticks out from the side of the nucleus and looks a lot like a coral growth. It is broken down into the smooth ER and the rough ER. The rough ER is the part that is closest to the nucleus. It is rough as it contains the Ribosomes. These are little factories that take the genetic blueprints from the nucleus and turn into proteins to do work. The rough ER is like the industrial manufacturing sector of the cell. It is where all the Ribosomes make all the proteins. There are some Ribosomes that float in the cytoplasm, but they are there for specific proteins that are needed there. The smooth ER makes the lipids for the cell so that it can make membranes as it needs them.

The Golgi Apparatus or Golgi Body sits in the cytoplasm of the cells and acts like the post office. All the proteins that are made by the Ribosomes get sent to the Golgi body. Some of these proteins will be used inside the cells while others will need to be taken to be displayed on the cell surface. Others will need to be secreted by the cell. The Golgi Body takes these proteins and marks them for delivery to their proper destination.

The Mitochondria is located in the cytoplasm of the cell. It acts at the power plant of the cell. It takes in sugar and breaks it down to create energy in the form of Adenosine Triphosphate (ATP) which the cell uses to power all its functions. The mitochondria has its own DNA. This comes from the mother. Everyone gets the exact same mitochondrial DNA as their mother. This is because the egg contains a mitochondria of the mother, but the dad's sperm has nothing but a copy of his genetic information. The proteins made by the mitochondrial DNA are used for breaking down the sugar. Genetic defects in this DNA will lead to disorders in making energy from sugar and will be passed from mother to child.

The Lysosome takes in the nutrients for the cell in the form of proteins from the food we eat. It breaks them down into the basic amino acids in the process called catabolism. These basic amino acids can then be used by the Ribosomes to build new proteins the cell needs in the process called anabolism.

The Proteasome acts like the recycling center of the cell. The cell is constantly making new proteins. The old proteins need a system to be broken down so the cell can reuse those amino acids to build new proteins. This is done by the proteasome. When a protein is no longer needed, it will get tagged for destruction in a process called ubiquitination. Once that protein is tagged for destruction, it will get loaded into the proteasome and broken down into small fragments of amino acids called peptides. This part is important in immunology. These peptides can be screened by an immune molecule called MHC. This will pick up pieces of these peptides and display them on the cell surface. This allows the immune system to see these self peptides and know all is well inside this cell. When a pathogen invades a cell, parts of its proteins will get broken down by the proteasome. These will be picked up by the MHC and taken to the surface. These foreign peptides will be an alarm to the immune cells.

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Bacteria

We learned that all living things are made up of cells. Those cells can be broken down into two major classifications with the Prokaryotic and the Eukaryotic cells. The major difference between a Prokaryotic cell and a Eukaryotic cell is the membrane around the nucleus. A prokaryotic cell has no membrane to create a nucleus around the DNA. As a matter of fact, the prokaryotic cells don't have any membranes around any of their organelles inside the cytoplasm. The eukaryotic cells have a membrane around the nucleus and around many of its organelles. The prokaryotes make up all the bacteria on Earth while eukaryotes make up all the plants and animals. The other major difference between prokaryotic cells and eukaryotic cells is how they reproduce. The bacteria use a process called binary fission while eukaryotic cells use the process called mitosis. Prokaryotes have one chromosome while eukaryotes typically have multiple chromosomes. All bacteria have a single chromosome that is circular double stranded DNA.

Bacteria are the most abundant life on earth. They outnumber us humans by more than 1,000 fold. Each person has bacteria living on and in them. We call these friendly bacteria commensal species or flora. The average person probably has more bacteria living on their skin and in their gut then they actually have human cells.

Bacteria are prokaryotes as they have no nucleus to protect their DNA. They don't have any membranes to protect any of their organelles. They have a region of the cytoplasm where the DNA hangs out called the nucleoid. They have a single circular chromosome that is double stranded DNA. Some bacteria will have a second segment of DNA called a plasmid. The chromosome of the actual bacteria will be on the bacterial chromosome which encodes all the genes for that bacteria, but other genes can be kept and shared on the plasmid. A bacteria with a plasmid is called a F positive (F+) bacteria which stands for fertility factor. It can transmit that plasmid to other bacteria. This is where the genes for antibiotic resistance reside in bacteria. It also allows them to pass this trait to other bacteria by horizontal gene transfer.

Bacteria have three ways to transmit their genetic information to other bacteria in the process of horizontal gene transfer. They are Transformation, Transduction, and Conjugation. The process of transformation occurs when a bacteria dies and its DNA is left for another bacteria to come along and pick it up. This allows the bacteria to incorporate that other bacteria's DNA into its own. The process of transduction is when a virus called a bacteriophage comes along and picks up a piece of bacteria DNA then carries it to the next bacteria as it spreads. The last is conjugation and happens when a bacteria with a F plasmid connects to another bacteria and transfers a copy of its plasmid to the other bacteria.

Bacteria have a cytoplasm and some of the same organelles as eukaryotic cells like Ribosomes. They have a plasma membrane that is a phospholipid bilayer like human cells. There are some layers around the outside of bacteria that do make it different. There is a layer of hard peptidoglycan shell that covers the membrane. This is where we will distinguish between Gram positive and Gram negative bacteria.

The Gram naming of bacteria comes from gram staining which is used to detect the difference between these two different kinds of bacteria. The gram negative bacteria have a thin layer of peptidoglycan coating (usually 3 layers) then another outer membrane. This makes them smoother. The gram positive bacteria will have many layers (as many as 40) of the strong peptidoglycan shell. This is a major difference in how we treat these bacteria and how our immune system treats them.

The membrane of the bacteria will have several structures that are important to their immune recognition. The first is the Lipopolysaccharides (LPS) and the Lipoteichoic Acid (LTA). These structures are made up of sugars and fatty acids that stick out from the cell's inner plasma membrane. They are highly specific to gram positive and gram negative bacteria. The immune system cells have receptors specifically for these LPS and LTA antigens. LPS is a sign of a gram negative bacteria and will trigger specific Toll Like Receptors. The LTA is a sign of gram positive bacteria and triggers different Toll Like Receptors.

The last major part of a bacteria is the flagella. All bacteria have a flagella, but not all flagella are the same. There are different types of flagella. The key role of the flagella is motility. It's also one of the dead giveaways to the immune system as human cells do not have a flagella.

Bacteria are classified and named by their structure and family The first part of the name comes from how that bacteria clusters. The second part of the name comes from the shape of the bacteria. The final part of the name is the actual bacteria name. For example Staphylococcus Aureus. The Staph comes from the cluster, the coccus comes from the shape and the Aureus is the actual bacteria name.

The shape of bacteria fall into a round shape which is called Cocci, rod shaped which are called Bacilli and corkscrew shaped spirochaetes. You will see this nomenclature used in their naming like Staphylococci. This means that bacteria is round. This name comes after the name for clustering and before the actual name of the species such as Aureus. The same naming works with Streptococcus Pyogenes which is another round bacteria.

So now that we know how to name a bacteria due to its shape, we can look at the naming of bacteria according to how it clusters like Strep and Staph. This refers to how these bacteria grow in a colony. The Staph bacteria will grow in clusters that look like grapes. The Strep grows in long chains that look like a string of beads. There is also a Neisseria naming for certain bacteria that grow in pairs of two. Nesseria Meningitidis is a bacteria that grows in clusters of two bacteria.

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Viruses

Viruses are much smaller than bacteria in general with few exceptions. They are just genetic information packed up into a delivery package. They invade cells and release their genetic information. This takes over the cell and reprograms it to produce more of the virus. The virus lacks any of the attributes of a living organism when it's not inside a cell, but it has all them when it's inside the host cell. This is part of the debate of whether or not they are alive.

Viruses come with both RNA and DNA genomes. They are actually broken down into 7 classifications on a Baltimore Scale based on the type of DNA or RNA they use. Class 1 viruses are single stranded DNA while Class 2 viruses are double stranded DNA. The other class of virus that has DNA is the class 7 which is part DNA and RNA like Hepatitis B. The RNA viruses come in 4 different classifications. The class 3 are double stranded RNA. The class 4 and 5 are single stranded RNA, but one uses the positive strand and the other the negative strand. The last one is class 6 which is the retroviruses. They are RNA viruses that copy themselves into DNA and insert themselves into the host genome. Retrovirus need special mention as they are used in gene editing like Lentivirus. Only a Retrovirus that includes the Reverse Transcriptase and Integrase can insert into the Genome. Sometimes DNA based viruses can integrate through recombination and integration into the genome. These are typically the viruses that lead to cancer as by doing so they can alter gene expression or cause mutations.

Viruses come in different packages called capsids. The capsid is made up of proteins. Some of the most basic viruses are made up of a capsid that is a single protein repeated dozens of times. Some of the more complex viruses use multiple proteins to make their capsid. There are three basic structures of capsids: icosahedral, helical and complex. The icosahedral uses small triangle facets to form its shell and they look like the 20 sided dice you see in D&D. The helical strings together a chain of proteins like beads into a helix like coil. They tend to look like a Slinky which can coil up to make a tube-like structure. The last uses a combination of both an icosahedral and helical together. A bacteriophage is a classic combination which has an icosahedral capsid attached to a helical tube.

Some viruses have a membrane that surrounds the capsid. We call these enveloped viruses. Not all viruses will have a membrane, but some do. Those without the membrane tend to be more hardy at surviving outside the body while the membrane viruses do better at blending in with our cells and avoiding immune detection.

All viruses have proteins on their membrane that allow them to bind to specific cell receptors. We call this tropism. We call these proteins ligands, and they bind to receptors on the host cell. Hepatitis has ligands for receptors on liver cells. Therefore, it has tropism for the liver. The influenza virus has a ligand that binds to receptors in the upper and lower respiratory tract giving it tropism for the sinuses and lungs. Every virus has ligands that make them bind to only specific cells. That is the concept of tropism in virology.

Once the virus is attached to the cell, it has to make an entry. There are many ways viruses can use to make entry, but the most common two are receptor mediated endocytosis and fusion. With receptor mediated endocytosis, the receptor binding triggers the cell to willfully take the virus into itself using a natural cell process of endocytosis. The other way is the virus has a fusion protein that binds to the cell membrane and pulls the virus and cell membranes into contact causing them to fuse together.

Once the virus is inside the cell, it will undergo the process of releasing the genetic material from the capsid. This is where so many viruses differ. They all have different strategies to get out of their capsid. Many use the high level of enzymes in the lysosomes to help them release from their capsid.

The genetic material will go to work taking over the cell's natural machinery. For the DNA viruses they will go into the nucleus where they can use the machinery there to transcribe their own DNA into proteins and even duplicate their DNA to package into new virus particles. The RNA viruses will typically bring their own RNA polymerases (when needed) and use those to produce RNA for direct translation by the Ribosome into proteins.

Once the virus copies its genetic material and uses the Ribosomes to build new capsids, it can take two approaches to get outside of the cell. The first is called the lytic cycle where the virus just keeps making more and more new virus particles until the cell can't hold any more and bursts releasing all the virus particles to go and infect other cells. The other way is called budding. The virus will assemble itself at the membrane of the cells releasing the virus particles into small membrane coated particles. This process is called budding.

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Parasites

Parasites are very rare in the developed world in humans. Our pets can get worms as we often give them antiparasitic medications for these infections. Parasites are broken down into intracellular and helminths. The intracellular parasites include things like Toxoplasma, Plasmodium, Trypanosoma, Leishmania. The other type of parasite is the helminths which we call worms. Parasites enter the body as eggs through food or by a vector like a bug bite. Those that enter by bug bites are single cell parasites. They get into a cell like a virus where they reproduce and live. This can make them very difficult to treat. The parasites that enter through food often live in the GI tract and release eggs. They can't reproduce inside the person they are infecting. The disease burden is often limited by the level of exposure. Intestinal parasites release eggs that are passed in waste to go on to infect others.

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Fungi

Fungi are eukaryotic cells unlike human cells. They are plant-like organisms which produce spores, but don't have chloroplasts like other plants. They typically like dark and wet environments and play a key role in breaking down organic compounds into basic nutrients. Some of these fungal pathogens can be harmful to humans like mold, athlete's foot, and ringworm. The key thing to know about fungal infections is they don't respond to antibiotics which are specifically used for bacteria. They have their own class of medications called antifungal medications. Some fungi can be useful like baker's yeast. We use this in cooking to ferment sugars. Others can be very deadly like Mucormycosis which is called black mold.

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