Molecular basis of diseases Flashcards
What is a disease?
According to the Oxford English Dictionary, a disease is “a condition of the body, or some part or organ of the body, in which its functions are disturbed or deranged.”
What are the main types of diseases?
- Infectious diseases (e.g., tuberculosis, flu, candidiasis, malaria)
- Injuries (e.g., fractures)
- Diseases caused by environmental factors (e.g., silicosis)
- Genetic mutations (e.g., inherited cystic fibrosis, acquired cancer)
- Multifactorial disorders (e.g., heart disease, schizophrenia)
Why is it important to understand the different types of diseases?
It aids in diagnosis, understanding the causes, targeting specific interventions, and developing treatments based on molecular mechanisms.
What is the “Chain of Infection”?
It includes:
- Susceptible Host
- Portals of Entry
- Modes of Transmission
- Pathogens
- Reservoirs
- Portals of Exit
How do viruses infect cells?
Viruses bind to host cells, enter them, and incorporate their genomes into host DNA to replicate, often damaging or killing the host cell in the process.
What are examples of viral infections?
- Influenza virus (Flu)
- SARS-CoV-2 (COVID-19)
- HIV (AIDS)
Describe Gram-positive vs. Gram-negative bacteria.
- Gram-positive: Thick peptidoglycan cell wall with teichoic acid; less resistant to antibiotics.
- Gram-negative: Thin cell wall with an outer membrane; more resistant due to porins and drug pumps.
What is Tuberculosis (TB)?
TB, caused by Mycobacterium tuberculosis, is a bacterial infection primarily affecting the lungs, with over one-third of the world population infected.
What are monogenic disorders?
Mutation in a single gene produces a dysfunctional protein that results in clinical disease
What causes atherosclerosis in coronary heart disease?
High LDL levels lead to plaque formation in arteries, narrowing them and increasing the risk of blood clots and heart attacks.
What are multifactorial diseases?
Diseases influenced by both genetic and environmental factors, such as schizophrenia, diabetes, Alzheimer’s, asthma, and heart disease.
Describe the molecular basis of Type 2 Diabetes (T2D).
T2D involves insulin resistance or insufficient insulin production, often influenced by lifestyle and genetic factors, leading to high blood glucose levels.
What is the link between obesity and T2D?
Excess fat, particularly abdominal, raises free fatty acid levels in the blood, which is linked to insulin resistance and can exacerbate T2D.
Why is it crucial to understand the molecular basis of diseases?
It allows for the identification of drug targets, aiding in the development of treatments that can precisely address underlying molecular dysfunctions.
What is precision medicine?
A medical approach that uses genomic, molecular, and environmental information to tailor treatment and develop drugs for specific patient needs.
Describe influenza virus infection
- Influenza virus binds to cell-surface sialic acid receptors through its surface glycoprotein hemagglutinin.
- After intracellular replication, a cell-surface neuramidase cleaves sialic acid from the cell membrane allowing viral escape.
Describe SARS-Cov-2 infection
- The spike protein of the virus binds to the cellular receptor ACE2 to facilitate the entry of the virus.
- Viral RNA undergoes replication and transcription to mRNA.
- The mRNA is translated into viral proteins.
- New viral proteins are assembled in the ER and Golgi apparatus.
- New virus particles (virions) are released through vesicles, and the virus produces numerous harmful effects.
Describe HIV infection
- HIV binds to host CD4 via its envelope glycoprotein gp120.
- Further binding to chemokine receptors CCR5 and CXCR4 allows a transmembrane protein gp41 to achieve cell fusion.
- Entry of the viral capsid is followed by the uncoating of the 2 single-stranded RNA molecules.
- Host DNA polymerase forms dsDNA, which is integrated into the host genome.
- Regulatory proteins control the transcription of viral RNA and mRNA from the DNA template. Viral proteins and RNA are reassembled into a capsid and released from the cell, causing its death.
- Destruction of T lymphocytes is a consequence of CD4 targeting and is the cause of immunodeficiency.
Familial Hypercholesterolaemia (FH)
- Genetic disorder characterised by high cholesterol levels, specifically LDLs.
- Mutation in the LDLR gene that encodes the LDL receptor protein which normally removes LDL from the circulation.
- LDL is a major cholesterol carrier and is taken up into tissues by receptor-mediated endocytosis.
- LDL contains apoprotein B which acts as a ligand for the LDL receptor. The interaction is between positively charged amino acids (arg) on the apoB and negatively charged amino acids in the binding site of the LDL receptor.
Lung cancer
- Non-small cell lung carcinomas (NSCLC) account for 80-85% of lung cancer. There are three types: adenocarcinoma, squamous cell carcinoma, large cell carcinoma
- Lung cancer is initiated by the activation of multiple oncogenes or inactivation of tumour suppressor genes.
- The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion. Mutations and amplification of EGFR are common in non-small cell lung cancer.
- Mutations in lung cancer: K-Ras G protein, MET, LKB1, B-Raf, ALK, EML4-ALK
Different human disease models
- 2D cell culture
- Organoid
- Bioengineered tissue model
- One-organ model
- Multi-organ model
