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BMS3031 - Molecular mechanisms of disease - S1 2026

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In the early 1970s, tricyclic antidepressants were

introduced which inhibited the reuptake of both noradrenaline and

serotonin. Whilst effective, these drugs

had many side effects and researchers sought to create antidepressants that

selectively enhanced serotonin neurotransmission. At that time, techniques such as

computer-aided design or large-scale high-throughput screening were not widely

available.

Which approach most likely led to the discovery of the first

selective serotonin reuptake inhibitors?

Screening thousands

of compounds using automated high-throughput assays

❌

Systematic structural

modification of existing drugs with weak serotonin reuptake blocking properties

to improve efficacy

✅

The compound was

likely discovered through serendipity

❌

Isolating

biologically active serotonin-modulating molecules from microbial sources

❌

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A new oral anticoagulant has recently received regulatory

approval for stroke prevention in patients with atrial fibrillation. Within the

first year of clinical use, clinicians reported that patients with peripheral

arterial disease experienced unexpected improvements in their symptoms while

taking the medication. This effect was not observed during earlier clinical

trials.

What is the most likely reason for this potential new indication

being observed during post-marketing surveillance?

The anticoagulant is

administered more frequently in everyday practice

❌

The anticoagulant is

used by a broad patient population with multiple comorbidities

✅

Only single,

short-term doses of the anticoagulant are administered

❌

Administration of the

anticoagulant is tightly controlled through study protocols

❌

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EL-12 is an active drug and metabolised by CYP2C19. 26% of the population are classified as CYP2C19 poor metabolisers.

In these patients, the standard dose of EL-12 is likely to result in:

worsening of depression symptoms with decreased risk of arrhythmia

❌

Increased risk of side effects such as arrhythmia but reduced therapeutic outcomes

❌

reduced effectiveness of the drug and with decreased risk of arrhythmia

❌

improvement in depression symptoms with increased risk of arrhythmia

✅

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A new antidepressant is undergoing clinical development. At

one stage, the study is designed to determine whether the drug has a clinically

meaningful effect compared with no active treatment, while minimising bias and

placebo response in patients with diagnosed depression.

Which study feature is most essential at this stage of

development?

Administration of a

single dose to assess tolerability

❌

Conducting the study

at multiple international centres

❌

Inclusion of a

placebo control

✅

Enrolment of healthy

volunteers

❌

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During the COVID-19 pandemic, several vaccines were developed

and made available to the public in record time. Despite the usual lengthy

process for vaccine development, these vaccines completed pre-clinical and

clinical testing, and received regulatory approval much faster than typical.

Which factor most plausibly explains how this accelerated

development was achieved?

Pre-clinical safety

studies were skipped to save time

❌

Regulatory approval

from authorities such as the Therapeutic Goods Administration (TGA) was not

required

❌

Only Phase I clinical

trials were conducted

❌

Prior knowledge of

related coronaviruses was used to inform vaccine development

✅

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Which statement best reflects the data shown below?

* 1-Mo = 1 month, 18-Mo = 18 months

The 18-Mo mice who received both MitoQ & BGP-15, provided enhanced protection against chromosomal misalignment than either treatment on its own

❌

Oocytes from old mice (18-Mo) have the same rate of chromosome misalignment as young mice

Treatment with either MitoQ or BGP-15 reduces chromosomal misalignment in old mice (18-MO)

MitoQ significantly improves the percentage of young oocytes (1-Mo) with aligned chromosomes

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The figure below shows the effect of age on the percentage of embryo transfers that result in live births for assisted reproduction transfers (ART) using fresh embryos from a woman’s own vs donor eggs. Which of the following conclusions can be made based on this data?

Both maternal and paternal factors influence ART outcomes with age

❌

Success of ART is dependent on the maternal hormonal environment

❌

Donor eggs should always be used for ART treatment

❌

Oocyte quality decreases with age

✅

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Which statement best reflects the data shown below?

* 1-Mo = 1 month, 18-Mo = 18 months

Oocytes from old mice (18-Mo) have the same rate of chromosome misalignment as young mice

❌

BGP-15 significantly improves the percentage of young oocytes (1-Mo) with aligned chromosomes

❌

MitoQ and BGP-15 protect oocytes from old mice from chromosome misalignment

✅

In eggs from old mice (18-Mo), a combination of MitoQ and BGP-15 is significantly better than either BGP-15 or MitoQ alone

❌

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Successful fertilization and early embryonic development

require high levels of metabolic activity within the oocyte. These processes

depend on ATP availability to support spindle formation, chromosome

segregation, and early cell divisions. Mitochondrial performance is therefore a

key determinant of oocyte quality.

Which finding best explains why mitochondrial

function is essential for oocyte competence and early development?

Oocytes

rely primarily on anaerobic ATP production rather than mitochondrial metabolism

❌

Increased

mitochondrial number with age compensates for declining mitochondrial

efficiency

❌

Ion

fluxes at fertilization fully restore developmental competence independently of

mitochondrial activity

❌

Efficient

mitochondrial ATP production supports the energy-intensive processes required

for fertilization and early embryonic cell divisions

✅

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Oocyte ageing is associated with an increased risk of

aneuploidy, contributing to infertility and pregnancy loss in older females.

Chromosomal cohesion during meiosis is critical for accurate segregation, and

this process relies on proteins such as cohesin and separase.

Which mechanistic scenario best explains why

ageing oocytes are more prone to aneuploidy?

Ageing

oocytes maintain normal cohesin levels but low levels of separase, leading to

excessive oxidative damage that increases the risk of aneuploidy

❌

Decreased

separase activity in older oocytes leads to failure of anaphase progression in

meiosis I, halting all oocytes before completion

❌

Reduced

levels of cohesin in older oocytes weaken chromosome cohesion, which can lead

to premature separation of homologues or sister chromatids during meiosis

✅

Increased

cohesin in older oocytes causes chromosomes to stick together excessively,

impairing segregation

❌

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