1: Mammalian cell
Mammalian cells have many different components that must come together for a cell to function
correctly and survive.
• High compartmentalised- highly complex subcellular organisation with multiple membrane
bound organelles
• Allows segregation of biochemical process is a way that they can proceed under optimal
conditions without affecting other cellular processes.
Many problems can happen within in the cell such as viral or bacterial infection as well as disruption
of processes that can cause disease:
• Genetic disorders
• Cancer- dysregulated cell division
Features of a cell
• Plasma membrane-lipid bilayer that surround cell and represents major interface between a
cell and its environment and allows transportation through channels. Has membrane bound
receptors that bind to ligands e.g. cytokines to be taken up to trigger change in cell behaviour
• Nucleus- membrane bound organelle approx. 5 micrometres and contains DNA. Nucleus has
distinctive organisations with non-membrane bound structures such as nucleolus, PML bodies
and Cajal bodies
• Cytoplasm- all the cell except the nucleus. The cytosol is the soluble part of the cytoplasm. The
cytosol is the site of many important biochemical processes
• Cytoskeleton- includes microtubules- function is cell division, determines positions of
organelles and involved in intracellular transport. Actin filaments- determine shape of cell
shape, intermediate filaments- provide mechanical strength
• Mitochondria- site of ATP production as well as other function such as apoptosis. Double
membrane bound and 1-2 micrometre in length.
• Secretory pathway- combination of organelles: RER, SER and Golgi apparatus. ER functions as
the site of protein synthesis and folding of secreted proteins. SER is site of lipid synthesis.
• Lysosomes- hydrolyses of complex macromolecules into their components so they can be
recycled into amino acids from proteins. Molecules are trafficked to lysosomes by the
endocytic pathways including extracellular material via autophagy
• Peroxisomes-small membrane bound, contain enzymes that degrade hydrogen peroxide
(h2o2). Functions include role in fatty acid metabolism (beta-oxidation).
Cell Biology of Disease- MICR2120 Page 1
, 2: The Nucleus
• Membrane bound organelle that contains most of cell genetic information and is therefore the control centre
• Compartmentalisation
○ Controls activities inside and outside the cell
○ Nucleus separates translation and transcription
○ Separates the nuclear and cytosolic enzymes- needed to protect DNA from harsh cytosolic environment
Nucleus structure
• Nuclear envelope- double membrane
• Nuclear membrane- impermeable to large molecules have pores allows translocation and movement of molecules across envelope
• Nuclear lamina- meshwork that adds mechanical support
• Subnuclear bodies- made up of unique proteins, RNA molecular and particular parts of the chromosomes
Visualisation of nucleus
Fluorescent micrograph allows cell to be stained with markers. HeLa (immortal cell line) is stained with markers for nuclear pore complexes
(NPC, red), nucleolus (green) and chromatin (blue).
Nuclear membrane/envelope
The nuclear membrane is a double lipid membrane that is a physical barrier to separate contents from cytoplasm. The outer-membrane
interacts with RER and the inner nuclear membrane has several INM- inner nuclear membrane- proteins which associate with the nuclear
Cell Biology of Disease- MICR2120 Page 1
,interacts with RER and the inner nuclear membrane has several INM- inner nuclear membrane- proteins which associate with the nuclear
lamina. The inner nuclear membrane is connected to the nuclear lamina via proteins called intermediate filaments
Nuclear lamina
• Full of proteins and filaments which give nucleus its shape and structure.
• Nucleus is a spherical structure and lamina gives it this shape and chemical support.
• Dense approx. 30-100nm thick
• Proteins associated with the nuclear lamina are linked to genetic disorders called LAMINOPATHIES
Laminopathies
A group of rare genetic disorders due to mutations in genes encoding proteins of the nuclear laminas and the first laminopathies were
discovered in late 1990's via confocal microscopy (3D image) was used to identify patients with these disorders. The characteristic of
laminopathies are:
• dysregulated and abnormal nuclei within the cell
• not smooth in structure and misshaped which is a classic sign
• variety if clinical symptoms
○ Skeletal muscular dystrophy
○ cardiac muscular dystrophy
○ Lipodystrophy- abnormal distribution of fat
○ Progeria- premature aging
• Main mutations in Lamin A/C and nuclear lamina associated proteins like emerin cause it.
• Mutations in genes might lead to defects in:
○ Filament assembly
○ Poor attachment to nuclear envelope
○ Jeopardises nuclear envelope stability in physically stressed tissues like:
▪ fibres
▪ bone
▪ skin
▪ connective tissue
• There is not cure and treatment.
1st laminopathy: Emery-Ereifuss muscular dystrophy
• Condition that affects skeletal muscles and cardiac muscles.
• Earliest features are joint deformities called contractures which restrict their movement of joint causing an abnormal stance
• This is continual throughout their life
• Most experience slowly progressive muscle weakness and wasting
• Cardiac conduction defects- heart problems due to abnormalities of electrical signals that control heart beat
Cell Biology of Disease- MICR2120 Page 2
, 2nd laminopathy: Hutchinson-Gilford Progeria Syndrome- HGPS
• A disease in which physical aspects of aging are accelerated
• Most patients with HGPS have a point mutation in the LMNA gene
• Mutation results in translation of a lamin A lacking 50 amino acids
• Mutant protein called LAD50 is incorporated in the nuclear lamina leading to:
○ Mechanical defects
○ Thickening of the lamina leading to loss of peripheral heterochromatin and increased DNA damage
• No cure
Organisation of genetic material
• There are 23 pairs chromosomes
• 22 pairs are autosomes and 23rd pair is sex chromosomes
• DNA organises the chromosome very well into discrete positioned 'chromosome territories'.
• Specific localisation of each pair of chromosome.
• How this occurs is still not known
• Maybe specific proteins bind to chromosome leading them to a particular position in the nucleus
• Each human cell contains about 2m of DNA and must be fit in a very organised space.
Histone proteins are used to compact the chromosomes. There are two types of histones:
1. Euchromatin-
○ DNA wrap around histone proteins forming nucleosomes like beads on a string.
○ Transcription factors are able to get to the DNA.
2. Heterochromatin-
○ very tightly compacted and less transcription factors able to get to DNA.
○ Mostly inactive DNA consists of:
□ constitutive heterochromatin- never expressed
□ facultative heterochromatin- differentially expressed.
These euchromatin proteins and heterochromatin is also organised in the nucleus. The darker area is heterochromatin and lighter
euchromatin.
Cell Biology of Disease- MICR2120 Page 3
Mammalian cells have many different components that must come together for a cell to function
correctly and survive.
• High compartmentalised- highly complex subcellular organisation with multiple membrane
bound organelles
• Allows segregation of biochemical process is a way that they can proceed under optimal
conditions without affecting other cellular processes.
Many problems can happen within in the cell such as viral or bacterial infection as well as disruption
of processes that can cause disease:
• Genetic disorders
• Cancer- dysregulated cell division
Features of a cell
• Plasma membrane-lipid bilayer that surround cell and represents major interface between a
cell and its environment and allows transportation through channels. Has membrane bound
receptors that bind to ligands e.g. cytokines to be taken up to trigger change in cell behaviour
• Nucleus- membrane bound organelle approx. 5 micrometres and contains DNA. Nucleus has
distinctive organisations with non-membrane bound structures such as nucleolus, PML bodies
and Cajal bodies
• Cytoplasm- all the cell except the nucleus. The cytosol is the soluble part of the cytoplasm. The
cytosol is the site of many important biochemical processes
• Cytoskeleton- includes microtubules- function is cell division, determines positions of
organelles and involved in intracellular transport. Actin filaments- determine shape of cell
shape, intermediate filaments- provide mechanical strength
• Mitochondria- site of ATP production as well as other function such as apoptosis. Double
membrane bound and 1-2 micrometre in length.
• Secretory pathway- combination of organelles: RER, SER and Golgi apparatus. ER functions as
the site of protein synthesis and folding of secreted proteins. SER is site of lipid synthesis.
• Lysosomes- hydrolyses of complex macromolecules into their components so they can be
recycled into amino acids from proteins. Molecules are trafficked to lysosomes by the
endocytic pathways including extracellular material via autophagy
• Peroxisomes-small membrane bound, contain enzymes that degrade hydrogen peroxide
(h2o2). Functions include role in fatty acid metabolism (beta-oxidation).
Cell Biology of Disease- MICR2120 Page 1
, 2: The Nucleus
• Membrane bound organelle that contains most of cell genetic information and is therefore the control centre
• Compartmentalisation
○ Controls activities inside and outside the cell
○ Nucleus separates translation and transcription
○ Separates the nuclear and cytosolic enzymes- needed to protect DNA from harsh cytosolic environment
Nucleus structure
• Nuclear envelope- double membrane
• Nuclear membrane- impermeable to large molecules have pores allows translocation and movement of molecules across envelope
• Nuclear lamina- meshwork that adds mechanical support
• Subnuclear bodies- made up of unique proteins, RNA molecular and particular parts of the chromosomes
Visualisation of nucleus
Fluorescent micrograph allows cell to be stained with markers. HeLa (immortal cell line) is stained with markers for nuclear pore complexes
(NPC, red), nucleolus (green) and chromatin (blue).
Nuclear membrane/envelope
The nuclear membrane is a double lipid membrane that is a physical barrier to separate contents from cytoplasm. The outer-membrane
interacts with RER and the inner nuclear membrane has several INM- inner nuclear membrane- proteins which associate with the nuclear
Cell Biology of Disease- MICR2120 Page 1
,interacts with RER and the inner nuclear membrane has several INM- inner nuclear membrane- proteins which associate with the nuclear
lamina. The inner nuclear membrane is connected to the nuclear lamina via proteins called intermediate filaments
Nuclear lamina
• Full of proteins and filaments which give nucleus its shape and structure.
• Nucleus is a spherical structure and lamina gives it this shape and chemical support.
• Dense approx. 30-100nm thick
• Proteins associated with the nuclear lamina are linked to genetic disorders called LAMINOPATHIES
Laminopathies
A group of rare genetic disorders due to mutations in genes encoding proteins of the nuclear laminas and the first laminopathies were
discovered in late 1990's via confocal microscopy (3D image) was used to identify patients with these disorders. The characteristic of
laminopathies are:
• dysregulated and abnormal nuclei within the cell
• not smooth in structure and misshaped which is a classic sign
• variety if clinical symptoms
○ Skeletal muscular dystrophy
○ cardiac muscular dystrophy
○ Lipodystrophy- abnormal distribution of fat
○ Progeria- premature aging
• Main mutations in Lamin A/C and nuclear lamina associated proteins like emerin cause it.
• Mutations in genes might lead to defects in:
○ Filament assembly
○ Poor attachment to nuclear envelope
○ Jeopardises nuclear envelope stability in physically stressed tissues like:
▪ fibres
▪ bone
▪ skin
▪ connective tissue
• There is not cure and treatment.
1st laminopathy: Emery-Ereifuss muscular dystrophy
• Condition that affects skeletal muscles and cardiac muscles.
• Earliest features are joint deformities called contractures which restrict their movement of joint causing an abnormal stance
• This is continual throughout their life
• Most experience slowly progressive muscle weakness and wasting
• Cardiac conduction defects- heart problems due to abnormalities of electrical signals that control heart beat
Cell Biology of Disease- MICR2120 Page 2
, 2nd laminopathy: Hutchinson-Gilford Progeria Syndrome- HGPS
• A disease in which physical aspects of aging are accelerated
• Most patients with HGPS have a point mutation in the LMNA gene
• Mutation results in translation of a lamin A lacking 50 amino acids
• Mutant protein called LAD50 is incorporated in the nuclear lamina leading to:
○ Mechanical defects
○ Thickening of the lamina leading to loss of peripheral heterochromatin and increased DNA damage
• No cure
Organisation of genetic material
• There are 23 pairs chromosomes
• 22 pairs are autosomes and 23rd pair is sex chromosomes
• DNA organises the chromosome very well into discrete positioned 'chromosome territories'.
• Specific localisation of each pair of chromosome.
• How this occurs is still not known
• Maybe specific proteins bind to chromosome leading them to a particular position in the nucleus
• Each human cell contains about 2m of DNA and must be fit in a very organised space.
Histone proteins are used to compact the chromosomes. There are two types of histones:
1. Euchromatin-
○ DNA wrap around histone proteins forming nucleosomes like beads on a string.
○ Transcription factors are able to get to the DNA.
2. Heterochromatin-
○ very tightly compacted and less transcription factors able to get to DNA.
○ Mostly inactive DNA consists of:
□ constitutive heterochromatin- never expressed
□ facultative heterochromatin- differentially expressed.
These euchromatin proteins and heterochromatin is also organised in the nucleus. The darker area is heterochromatin and lighter
euchromatin.
Cell Biology of Disease- MICR2120 Page 3
