Example SAQs Flashcards
A man has lung cancer involving upregulation of EGFR, a receptor tyrosine kinase.
Explain how ligand binding to EGFR is converted into an intracellular
signal that promotes cancer development (4 marks)
- EGFR forms dimers (0.5 mark), activating the intrinsic kinase domain (0.5 mark)
- Autophosphorylation (0.5 mark) of tyrosine residues (0.5 mark) occurs
- Signalling proteins associate with the phosphotyrosines via SH2 domains (1 mark)
- Signalling cascades (mention any one of MAPK, Akt, JNK) (0.5 mark) activated which promote cell proliferation (0.5 mark)
Chimeric monoclonal antibodies such as ocrelizumab can be used in the treatment of cancer and autoimmune diseases such as rheumatoid arthritis.
Describe the steps involved in the production of monoclonal antibodies.
Outline the difference between monoclonal and polyclonal antibodies. (3 marks )
- Polyclonal Abs are polyvalent mixtures of antibodies produced by all plasma cell clones that reacted to a specific antigen. (e.g. bind to different epitopes). Found in serum of animals including humans during normal immune response. (1 mark
- mAbs are a single species of monovalent antibody, produced in vitro. (1 mark
- Immortalised hybridoma – fusion of a tumour cell with a specific lymphocyte clone. (1 mark
In the laboratory you use Western blotting to test that your cell line is expressing your protein of interest.
Describe the key steps involved in this technique. (7 marks)
- sample taken from cell culture
- cells broken open
- gel electrophoresis seperates the macromolecules
- seperated molecules blotted onto a second matrix
- membrane is blocked to prevent non-specific binding of antibodies
- probed with specific antibodies
- colour change produced
Explain how an action potential leads to synaptic transmission at the neuromuscular junction. (5 marks)
Presynaptic neuron is excited by an action potential, causing neurotransmitter vesicles to fuse with the presynaptic membrane and exocytose their contents into the synaptic cleft.
Neurotransmitters bind with receptors on the postsynaptic membrane and can cause an action potential to occur in the postsynaptic cell.
Eventually, the neurotransmitter molecules will be then degraded and repackaged/uptaken into the pre-synaptic membrane
Describe an example pathway of a nociceptive afferent neurons (5 marks).
Pain is detected by a nociceptor.
For example, the sensation of heat associated with spicy foods involves capsaicin, the active molecule in hot peppers. Capsaicin molecules bind to a transmembrane ion channel in nociceptors that is sensitive to temperatures above 37°C.
The dynamics of capsaicin binding with this transmembrane ion channel is unusual in that the molecule remains bound for a long time. Because of this, it will decrease the ability of other stimuli to elicit pain sensations through the activated nociceptor.
Describe the key steps of the NF-κB signalling pathway (5 marks )
- IKK complexes are phosphorylated upon receptor activation
- These IKK complexes then phosphorylate IκB proteins
- This leads to IκB ubiquitination and proteasomal degradation - this frees the NF-κB protein complexes
- Free NF-κB complexes then translocate into the nucleus and induce target gene expression
- induces the transcription of IκB, which establishes a negative feedback loop
A man ate a carbohydrate-rich meal in advance of a run to provide energy for cellular respiration.
Outline the key steps involved when cells use glucose to generate ATP during aerobic respiration (5 marks)
Glycolysis (0.5 mark) - Oxidation of glucose to pyruvate (0.5 mark)
• Oxidation of pyruvate by entry into TCA/Krebs cycle (0.5 mark) generates NADH and FADH2 (0.5 mark)
• Electrons transferred from NADH/FADH2 (oxidised) (0.5 mark) to oxygen (reduced) by respiratory/electron transfer chain activity (0.5 mark)
• During electron transfer, proton pumping by respiratory chain complexes (0.5 mark) generates protonmotive force (0.5 mark)
• Energy in protonmotive force used by ATPsynthase (0.5 mark)to drive ATP synthesis (0.5 mark)
Before the race, a man was sweating and had a raised heart rate due to activation of the sympathetic nervous system.
Describe the general structure of this branch of the nervous system and the main receptors involved in mediating its effects (5 marks)
- Has a short preganglionic neurone (ganglia located in sympathetic chains running alongside the spinal cord) and long post-ganglionic neurone reaching to the target organ (1 mark)
- Postganglionic receptors at neuronal synapses are nicotinic receptors (1 mark)
- Adrenergic receptors (alpha, beta) are present on target tissue (1 mark)
- Exception is sweat glands (0.5 mark), which are stimulated via muscarinic receptors (0.5 mark)
- Adrenergic receptors are G-protein-coupled receptors (GPRC) (1 mark)
Explain how an electrical impulse is transmitted to muscle cells at the neuromuscular junction and how skeletal muscle contraction is mediated (8 marks)
- Action potential causes voltage-gated (0.5 mark) Ca2+ channels (0.5 mark) to open, allowing calcium ions to move into the cell
- Acetylcholine (0.5 mark) is released into the synaptic cleft (exocytosis) (0.5 mark)
- Binds to nicotinic receptors (ligand-gated ion channels) on the motor end plate (1 mark)
- Depolarisation (0.5 mark) of end plate occurs (influx of Na+) (0.5 mark)
- Voltage-dependent (0.5 mark) Ca2+ channels (0.5 mark) open
- Calcium-induced calcium (0.5 mark) release from sarcoplasmic reticulum (0.5 mark) occurs
- Calcium binds to Troponin C (0.5 mark), exposing myosin binding sites on actin (0.5 mark)
- Cross-bridges (0.5 mark) form between myosin and actin, using ATP, and filaments slide over each other (0.5 mark)to shorten the sarcomere
Describe how blood clotting occurs in response to a cut in order to stem the flow of blood (8 marks)
- Constriction (0.5 mark) of blood vessels occurs to limit blood flow to the area (0.5 mark)
- Platelets are activated (vWF) (0.5 mark) and release substances to activate further platelets (positive feedback) (0.5 mark)
- Activated platelets aggregate (0.5 mark) and stick to collagen to form a loose platelet plug (primary haemostasis) (0.5 mark)
- Tissue factor (extrinsic) (0.5 mark) and contact (intrinsic) (0.5 mark) pathways of coagulation are initiated (secondary haemostasis)
- Both pathways involve a cascade of proteolytic conversions (0.5 mark) of inactive clotting factors to their active forms (0.5 mark)
- The two pathways converge on Factor X (0.5 mark), which is converted to active Factor Xa, which catalyses the conversion of prothrombin to active thrombin (0.5 mark)
- Thrombin catalyses the conversion of fibrinogen (soluble) (0.5 mark) to fibrin (insoluble) (0.5 mark)
- Fibrin polymerises and forms a mesh (0.5 mark) in which platelets and blood cells get caught, (0.5 mark) forming a clot.
Outline the types of molecules that are classed as biologics. Give specific examples of each type of biologic and for each type state the disease(s) they can treat (3 marks ).
- Proteins (0.5 mark), antibodies and oligonucleotides (0.5 mark).
- Give (1 mark) for each correct disease/treatment pair up to a total of (2 marks).
o Proteins: e.g. insulin – type 1 diabetes, tPA – stroke, EPO – anaemia or other valid option
o Antibodies: anti-TNF (OR infliximab/adalimumab/etanercept) – psoriasis/IBD. Anti-IL-23 – psoriasis or any valid
o Oligonucleotides: siRNA against α-synuclein - Parkinson’s disease or any valid
Manufacturing biologics can be problematic and there are advantages and disadvantages for using a particular expression system.
Explain why mammalian cell lines are often used as an expression system. (2 marks)
- Post-translational modification (1 mark) (including glycosylation and phosphorylation) so good for complex proteins.
- Any one of the following additional advantages (1 mark): high functionality, high compatibility with humans, low immunogenicity, non-human cells are not susceptible to human pathogens, high safety, regulatory permission for clinical use is easier than for human cells.
Describe the types of nociceptive afferent neurons and the types of sensory information they convey (5 marks).
Aδ fibres (1 mark) – large diameter, myelinated, fast transmission. Thermal or mechanical. Sharp, stabbing sensation (1 mark for correctly mentioning any feature) TRP channels (1 mark) e.g. TRPV1 – hot/capsaicin(chilli), TRPM8 – cold/menthol
C fibres (1 mark) – small diameter, unmyelinated, relatively slow transmission, Polymodal – mechanical, chemical, hot/cold. Dull aching session. (1 mark for correctly mentioning any feature)
Manufacturing biologics can be problematic and there are advantages and disadvantages for using a particular expression system.
Explain why mammalian cell lines are often used as an expression system. (2 marks)
Post-translational modification (1 mark) (including glycosylation and phosphorylation) so
good for complex proteins.
Any one of the following additional advantages (1 mark): high functionality, high
compatibility with humans, low immunogenicity, non-human cells are not susceptible to
human pathogens, high safety, regulatory permission for clinical use is easier than for
human cells.
