Molecular Cell Biology Flashcards
Biomarkers
A naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process or disease, can be identified
C-Reactive Protein (CRP)
- Measure of inflammation
- CRP is a general marker so isn’t useful for precise diagnosis
Anti Citrillunated Peptide Antibody
- Used to help diagnose rheumatoid arthritis
- ACPA is more definitive 95% of people who have it also have RA
Disease Specific Biomarker
- Uses
- Diagnose disease
- Monitor disease progression
- Predict response of treatment
- Prognostic - E.g. breast cancer and BRCA1 gene mutation
- Low risk
- High risk
Define Translational Research w Example
Translational medicine is an effort to build on basic scientific research to create new therapies, medical procedures, or diagnostics.
*Example: Ab block of TNF was thought to treat rheumatoid arthritis.
Define Stratified Medicine. 4 categories, explain use in practice.
Making sure you’re treating the patient with the correct medicines. based on genetic and epigenetic makeup.
Benefit + No Toxicity
Benefit + Toxicity
No Benefit + No Toxicity
No Benefit + Toxicity
- Depends on severity of disease and if benefits outweigh the risks, e.g. if indigestion tablets work but causes adverse reaction then it isn’t feasible.
Example of Stratified Medicine in Practice.
Breast cancer has many different biomarkers which can affect treatment.
- Estrogen receptor ER+ patients are treated with Tamoxifen
- HER2+ patients can be given herceptin
Cetuximab and K-RAS mutation
Cetuximab inhibits K-RAS which stops enzyme cascade leading to proliferation. A mutation in K-RAS allows it to evade the effects of the drug. Drug only works if the K-RAS gene is normal.
Personalised Medicine
Medical care in which the treatment is customised for an individual patient
CAR T-cell therapy mechanism
T-cells isolated via leukophoresis from patient with cancer. Introduce a gene into a lentivirus which causes it to present the antigen which is present on the cancer. they then expand T-cells up which respond to the cancer then it is administered to the patient. the T-cells go round and fight the cancer in the body
Gene Therapy: SCID.
- What is SCID?
- Why would it work?
- Treatment (Old and New)
Severe combined immunodeficiency.
-Rare inherited diseases where children are born with defective immune systems due to a gene mutation.
-It would work because it is a monogenetic defect so it is easier to correct.
-Old: Bone marrow transplants from donor, risk of rejection and latent viruses
New: take stem cells from Bone marrow and GM them using a virus then reimplant them
Differences between eukaryotic & prokaryotic cells
Euk/Prok size - 5microm/1-5microm nucleus - Yes/No Organelles - Yes/No Chromatin - Yes/No Cell wall - No(except plants)/ Yes Chloroplasts - Plants/ Some
Features of an animal cell with function
Nucleus - contains DNA in the form of chromatin.
Nucleolus - makes rRNA within the nucleus.
Mitochondria - makes energy
Endoplasmic reticulum - RER has ribosomes for protein synthesis
Golgi - involved in secretion
Intermediate Filament - involved in structure
Microtubule - Structure of the cell, part of cytoskeleton originate from centrosomes which are involved in cell division
Cell Membrane features
- Phospholipids
- Cholesterol
- Membrane Proteins
- Glycolipids (binding sites and cell specificity)
Functions of the membrane
- Define the boundary of the cell
- Regulate transport of solutes
- Mediate cell communication
What are Phospholipids made of
- Polar head
- Non polar hydrophobic tail
-Phosphate forms the head which can be attached to an R group.
the bend in the tail is important for its function in the membrane.
What affects the fluidity of the membrane?
- % of cholesterol
- How many bends in the hydrophobic tails
Permeability of the membrane
- Permeable
- Impermeable
- Semi-permeable
Permeable
- Gases
- Small uncharged polar molecules (Ethanol)
Semi-permeable
- Water
- Urea
Impermeable
- Large uncharged polar molecules (glucose)
- Ions
- Charged polar molecules (protein, aa, ATP)
Types of integral membrane proteins
- Transporters
- Anchors
- Receptors
- Enzyme
Types of Transporters and functions
Channel proteins - passive diffusion down conc gradient
Transporter mediated - for larger molecules
Active transport - uses energy to pump against conc gradient
Mitochondria - function and structure
- Function
to produce energy for the cell via ATP generation. - Structure
Permeable outer membrane
Less permeable inner membrane folded into cristae
Inside the inner membrane is the Matrix
How does the mitochondria make ATP?
- Pump is driving H+ into the intermembrane space forming a strong proton motive force which then drive the ATP synthase which is the turbine generating ATP from ADP and Phosphate
Golgi Apparatus function
modification, packaging and sorting proteins ready for secretion or for another organelle.
Lysosomes and peroxisomes
what are they and what’s their function?
Lysosomes
-Small irregular cytoplasmic vesicles
-Packed with degradative enzymes
-Principal sites of intracellular digestion
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Peroxisomes
-Small cytoplasmic vesicles
-Contained environment for reactive H2O2 generation
-The main function of the oxidation reactions is the breakdown of fatty acids
-Detoxify toxic substances such as ethanol (via catalase)
Cytoskeleton- functions
-Pulls the chromosomes apart during mitosis
-Drives and guides the intracellular traffic of organelles, proteins and RNA
-Supports the plasma membrane
-Enables some cells to move
controls cell shape
Three major components of the cytoskeleton
Microtubules -
20 nm diameter
Polymers of tubulin dimers
Organised from structures such as the centrosome
Form the spindle in mitosis
Important in cell shape and movement
Carry cargo-bearing motor proteins
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Intermediate filaments -
10 nm diameter filaments
Made of a family of fibrous proteins;
keratin filaments in epithelial cells,
vimentin in many other cells,
neurofilament proteins in neurones,
lamins within the nucleus.
Twisted into ropes and provide tensile strength
Needed to maintain cell shape
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Actin filaments - 7nm small, essential for movement, involved in moving proteins.
Can form contractile bundles and microvilli
May associate with myosin to form powerful contractile structures
Carry cargo-bearing motor proteins (e.g. myosin)
Which proteins are responsible for the movement of cargo across the microtubule tracts
Dyneins towards minus end (nucleus)
Kinesins towards + end (cell membrane)
Stem cells - characteristics
- Not terminally differentiated cells
- immortal cells
- Daughter cells have choice to remain stem or to differentiate
- Found where there is high turnover of cells
- Commonly occur at stem cell niches, this is important as the further the cell from the niche the more differentiated it is.
Embryonic stem cells - totipotent and pluripotent
Adult stem cells
Totipotent cells- can differentiate into any type of cell of the body plus the placenta and form an organism.
pluripotent can form any cell in the body
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Multipotent cells - can differentiate into different types of cell but of one cell lineage/ tissue type
Gut adult stem cells
- epithelial cells must be replaced frequently
- the pit of the crypt has stem cells that are constantly generating more cells
- replenishes the gut epithelium
other examples of stem cells
Skin and Haematopoetic.
Induced Pluripotent stem cells.
Adv vs Dis
Despecialise skin cells to make them pluripotent then specialise them
Advantages
-Cells taken from patient should not elicit immune response
-Fewer ethical issues
-Theoretically, any cell type could be replaced
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Disadvantages
-More basic research needs to be done on developmental pathways
-Transplanted stem cells could develop into cancer cells
Necrosis vs Apoptosis
Apoptosis (or programmed cell death) is the normal pathway. Signalling processes within the cell activate intracellular suicide proteases. These:
- Degrade intracellular structures and organelles
- Collapse the cytoskeleton
- Fragment the cell into mini-cells, which are engulfed by phagocytes for degradation.
** Apoptosis is neat and doesnt affect surrounding cells
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Necrosis
this is uncontrolled cell death which results in lysis of the cell releasing toxic enzymes to neighbouring cells.
