L2: Mechanisms of Disease - Discovery phase

Question 1

what are we made of?

Answer 1

cells -> tissues -> organs -> organ system

Question 2

what are the two basic structures of human cells

Answer 2

nucleus: DNA - houses our genetic information

Plasma membrane: proteins are on the membrane, where the drug acts

Question 3

where are genes in our body and what do they do

Answer 3

genes -> chromosomes -> nucleus -> cell

genes code for amino acids to make proteins

Question 4

explain DNA sturcture

Answer 4

double helix, made of four molecules; ATGC

Question 5

explain RNA structure

Answer 5

single stranded, made of four molecules;
AUGC

Question 6

how does RNA make amino acids to create protiens

Answer 6

a codon on the RNA -> amino acids -> peptide -> protein

Question 7

describe protien structure

Answer 7

proteins are huge chains of amino acids.
the chains are folded
shape = function

Question 8

what is the central dogma of biology?

Answer 8

DNA (genetic information) -> RNA (mRNA is DNA’s messenger) -> proteins (carry out cell functions).

Question 9

what is cancer? what are malignant tumours? what is metastatic cancer?

Answer 9

• Diseases of uncontrolled growth
• Includes spreading (malignant tumours):
• into normal tissues
• to other parts of the body (metastatic cancer)
• Normal growth control mechanisms dysregulated

Question 10

what are mestacies?

Answer 10

cancer that occurs outside its original primary site

Question 11

is cancer a single disease

Answer 11

No, its a group of over 100 different diseases

Question 12

how do we organize cancers?

Answer 12

– via tissue or organ of origin
– via mechanism of growth dysregulation
(aka pathways that lost control)

Question 13

How can you treat a group of over 100 different diseases with a single drug?

Answer 13

– you can’t - there is no one drug

• we tackle it by pathway. we may make a drug to re establish control when one pathway is dysregulated and see how that effects

Question 14

how is growth controlled in a normal cell?

Answer 14

usually the the cell grows depending on growth and stop signals. both are necessary to function to prevent the overgrowth of cells.

path of growth:
resting state -> listens for growth signals -> active growth machinery starts -> cell grows -> listens for stop signals -> active stop machinery starts -> cell stops growing.

Question 15

how is growth control lost in cancer? both ways:

Answer 15

One way:
The growth machinery is on overdrive - the cell is always growing, not listening to the external signals. There may be functional stopping signals, but it doesn’t keep up with the rate of growth. thus there is an overgrowth of cells.

another way:
lacking an effective stopping machinery. stopping signals may be present, but the listening molecule cannot hear the signal to stop or the machinery in the cell cannot stop. this can cause an overgrowth in cancerous cells.

Question 16

how do the control mechanisms get dysregulated (ie signals get disrupted to lead to an overgrowth in cell production)?

Answer 16

Mutations

Question 17

how do we get mutations?

Answer 17

• DNA errors in DNA copying (base pairs arent corresponded- can lead to errors in amino acids and protein formation)
• DNA damage

Question 18

what are the possible outcomes of mutations?

Answer 18

• No effect – the genetic code is redundant (creates the same amino acid), or the change occurred in a non- gene
• Base pair change causes a change in amino acid sequence – may or may not change the protein structure and function

Question 19

what causes genetic changes (list 6)?

Answer 19

• hereditary
• viruses
• UV radiation
• Smoking
• Chemicals
• cell dividing

Question 20

do cancer cells have genetic changes?

Answer 20

yes, the DNA of a cancer cell is different than the DNA of healthy cells in the cancer patient

Question 21

how does cancer relate to age

Answer 21

as you grow older you can accumulate mutations, thus increasing the probability of cancer. accumulation of mutations can be done due to increased exposure to environmental toxins, radiation, and errors in DNA replication.

Question 22

what are inherited mutations?

Answer 22

• Mutation present in the egg or sperm cell that formed the child.
• Since all the cells come from this first cell, this kind of mutation is in every cell (including eggs or sperm) and is passed to offspring

Question 23

what are acquired mutations

Answer 23

• mutation acquired during the persons life.
• It starts in one cell, and then is passed on to any new cells that are created from that cell.
• This kind of mutation is not present in egg or sperm cells, so it does not pass to offspring

Question 24

inherited vs acquired mutations: which has more of an effect

Answer 24

• Acquired mutations are much more common than inherited mutations.
• Most cancers are caused by acquired mutations.

Question 25

explain the cancer genome: what does it explain?

Answer 25

• one cell gains a mutation
• this cell then divides and grows
• this new cell may divide into multiple different cells
• all of these variations grow and mutate, creating a branched evolution of cells

this cancerous genome explains why:
* tumours are so hard to treat once they spread
* how they can become resistant to cancerous drugs
* and why it is so hard to find molecular markers to predict patients outcomes

-> all variations are different! cannot treat all of them the same

Question 26

what is chemotherapy?

Answer 26

• treatment that kills fast growing cells
• many very powerful drugs
• also kill fast-growing healthy drugs – con to it
• tend to be older drugs

Question 27

what is targeted therapy?

Answer 27

• uses modern cancer drugs
• therapy that is aimed at proteins that are only in cancer cells (unique), or that are far more abundant in cancer cells than normal cells
• Involves matching the correct drug to the correct molecular (protein, DNA) features of your unique tumour

Question 28

what is the difference between chemo and targeted therapy

Answer 28

chemo: kills both cancerous and healthy cells. older drugs

targeted: fights normal cells much more than normal cells. newer drugs

Question 29

explain the targeted cancer drug of herceptin

Answer 29

• proteins only on cancerous cells continuously shoot signals telling the cell to proliferate
• herceptin is a targeted antibody drug that can only bind to these proteins on the cancerous cells, blocking the protein from sending growth signals.

Question 30

describe our immune system (key molecule, role, main components)

Answer 30

White blood cells
* located in blood and lymphatic system

Role:
* attack viruses and bacteria
* can also attack cancer cells – if it can recognize cancer cells as foreign

Main components of human immune system:
* innate immunity (born with it)
* acquired immunity (you develop it when you are exposed to micro-organisms)

Question 31

explain the two types of immune cells

Answer 31

T cells (peptide binding)
* Can bind foreign peptides
* Some types of T cells destroy (kill) foreign -entities such as viruses
* Can kill cancer cells

B cells (antibody creation)
* Have the ability to create antibodies, which bind specifically to surfaces of foreign cells (eg microbes)
* Can create antibodies against surface proteins on cancer cells

Question 32

how do cancer cells avoid being destroyed by our immune systems

Answer 32

1. The genetics of the cancer result in a cancer cell that can’t be sensed (“seen”) by our immune system
2. The cancer cell might have proteins on the surface that turn off our immune cells (see course video)
3. The effect might be indirect – the cancer cells change the healthy cells in the tissue around the tumour. This change alters how the immune system deals with the cancer cell.

Question 33

what is immunotherapy

Answer 33

immunotherapy helps our immune system act better against the cancer, sometimes by counteracting these 3 mechanisms of how cancer cells avoid being destroyed by the immune system

(cancer cells r able to be sensed, proteins dont turn off the immune cells, the cancer isnt able to change the cells around the tumour thus allowing the immune system to interact with the cancer cell)

Question 34

red blood cell development pathway?

how does it evolve and where does it move?

Answer 34

stem cells -> mature red blood cells -> move through the blood stream -> enter tissues

Question 35

what is protein quaternary structure?

Answer 35

when two or more polypeptide chains come together to form one functional molecule with several subunits.

Question 36

what is hemoglobin and how is it made in the body?

Answer 36

hemoglobin: a quaternary structure where the 4 subunits cooperate so that the complex can carry for more oxygen from lungs to tissues

It is made up of alpha-globin and beta-globin

The HBB gene encodes beta globin protein. from both parents we get both proteins (alpha and beta) which combine to make hemoglobin

Question 37

What does sickle cell look like in the DNA, protein, and cell/tissue in comparison to a healthy person

Answer 37

Healthy:
- DNA: 2 working HBB genes
- protein: working beta globin combines with alpha goblin to make hemoglobin
- cell/tissue: the hemoglobin is round, flexible red blood cells that carry oxygen

sickle cell:
- DNA: 2 altered HBB genes
- protein: the beta globin is altered structurally, where it sticks to one another forming long fibers.
- cell/tissue: the red blood cells carry oxygen, but the fibres make them stiff and elongated.

Question 38

what are the two types of formations of drug

Answer 38

• small molecules: chemicals. most drugs are in this category.
• biologics: large biomolecules like proteins, genes, cell therapies, and vaccines. a few drugs in this category.