What The Hell? - The Cell

I wanted to give you a brief insight into some aspects of how cells work. This is a warm up for my next few blog posts about cancer. 

The Cell:
The cell is made up a whole lot of things (figure 1 shows just the bare minimum) which keep each cell and your body ticking over. Like a fried egg, the "yolk" of the cell is where all the genetic material is held. There are lots of things that want to degrade DNA in the "white" so DNA is kept in the "nucleus". RNA also spends some time in the nucleus and needs to be protected by "caps" on each end to stop it from damage (like a shoe lace). The "white" or "cytoplasm" is where everything else is. Mitochondria are the batteries for your cell. It is where all your energy is made. You have hundreds of mitochondria to power one tiny cell. Interestingly your mitochondria come completely from your mother. Ribosomes take the RNA made in transcription and translate this into a protein (see What the Hell? - Genetics for more detail).  The Endoplasmic Reticulum and Golgi Apparatus are important for the formation of lipids and some proteins and also modifying these proteins for specific functions (e.g. to sit in membranes etc.). The Cell Membrane is a double layered structure that maintains the cell's shape. It also controls very carefully what is allowed enter and exit the cell. For example, your cells need a constant balance of salts (sodium: Na+, potassium: K+ and chloride: Cl- also known as the membrane potential) to maintain ideal cell conditions. 

Figure 1: The Cell

Cell Signalling:
Cell signalling is an incredibly important process for cell survival. It allows cells to communicate to each other as well as letting the cell respond to the external environment. Cell signalling is when a cell responds to a stimulus (either external or internal) leading to a biological process (such as cell division, transcription or cell death). Stimuli include hormones or proteins from other cells. 
Figure 2 shows external cell signalling in it's simplest form. Imagine you are playing catch with a baseball.  A ball (a stimuli known as a ligand) is thrown and is caught by a catcher mitt (known as a receptor). When the ball is caught it "binds" to the mitt. When the receptor on the outer surface of the cell binds to the ligand it sends signal the membrane into the cell. The signal is passed on, activating pathways as it goes or it can be sent back out of the cell. In normal cells, ligands bind specifically to certain receptors. For example oestrogen will bind to the oestrogen receptor.  

Figure 2: Cell Signalling

Figure 3 shows three types of cellular signalling:

1. Autocrine: The cell releases a signal which activates receptors on it's own cell surface
2. Paracrine: The cell releases a signal which is picked up by cells directly neighbouring it.
   
3. Endocrine: The cell releases signals which are picked up by cells very far away (e.g. different organs).

Back to our example if you played catch, an autocrine signal will be playing catch on your own, paracrine signalling would be playing with your team and endocrine signalling would be playing against another team from a different part of the city. In the end you can still play catch but with different outcomes (autocrine and paracrine are very local, endocrine is global). 

Figure 3: Three types of signalling. Purple dot is the ligand.

Cell Division:
Cell signalling can lead to a very important process in the cell - cell division. Figure 4 shows what happens in cell division. Cell division is crucial for cells to grow and maintain. Cell division allows two "daughter" cells are made from one "parent" cell. The daughter cells are identical to the "parent" cell and each other. This is known as mitosis. Cells are highly complex so duplicating the entire cell structure is a complicated business. Cells go through a number of checks during each "phase" of cell division. It works like a traffic light system, if you have the right conditions and pass all the checks (no bad DNA damage, no bad gene mutations etc.) the cell gets the green light. If there is damage or something like that, the cell gets a yellow until the problem can be fixed. If there is something very wrong or the problems can't be fixed the cell gets a red light. This drives the cell to die. This traffic light system occurs at every check point. Proteins control these check points and the most recognisable cell division check point protein (which you may already know and will definitely hear about A LOT) is p53. One of the things p53 checks for is DNA damage. If the DNA is damaged you do not want the cell dividing. Letting DNA damage pass can lead to DNA mutations or whole chunks of DNA being lost or moving about the genome. A lot of DNA damage can be repaired by a range of different methods but if it can't be repaired p53 pushes the cell to die.

Figure 4: The Cell Cycle (Mathew L. Coleman, Christopher J. Marshall & Michael F. Olson. (2004). RAS and RHO GTPases in G1-phase cell-cycle regulation. Nature Reviews Molecular Cell Biology. 5 (5), 355-366.)

Cell Death:
If there is irreversible damage to a cell, a process called apoptosis will be triggered. This process leads to the death of the cell. Figure 5 shows what happens in apoptosis. To begin, a stress signal is detected by the cell. This can be internal, like DNA damage, or external like sudden changes to the cell environment. Other cells can also signal cells to die. Once a death signal is detected this starts a cascade of signals that ultimately leads to the cell breaking up into fragments which are then taken up by neighbouring cells or excreted from the body. The number of cells in your body remain quite constant so when new cells are made, older cells die. This prevents DNA damage and bad mutations from persisting in the body. 

Figure 5: Apoptosis. Photo Credit: Encyclopaedia Britannica Inc. Britannica Inc, E., Apoptosis. Available at: https://www.britannica.com/science/apoptosis [Accessed April 24, 2017].

These are just a few processes in the cell which will help me explain what cancer is and how we can treat/prevent cancer. 

Keep an eye out in the coming weeks for "What the Hell? - Cancer".


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And just for fun I wanted to include what an actual signalling pathway looks like. Figure 6 shows the AMPK signalling pathway. AMPK regulates growth pathways and is commonly lost or down regulated in cancer. This, you will be shocked and appalled to know, is a pretty simple straight forward signalling pathway.

Figure 6: AMPK Signalling. Photo credit Cell Signaling Technology Inc. Available at: https://www.cellsignal.com/contents/science-pathway-research-cellular-metabolism/ampk-signaling-pathway/pathways-ampk [Accessed April 24 2017]