Molecular Cell Biology and Disease

In these next few posts, I'll start getting into the applications of cell biology. This is all just getting our feet wet though- these following topics are the kinds of things that some people spend their whole lives working on.

Outline some of the major causes of molecular diseases.

There are lots of causes of molecular diseases. Cells are quite complex, and if any of the many processes that take place within the cell don't work properly, the consequences can range from benign to disastrous. Factors that can cause these processes to screw up in the first place include genetics, infectious and chemical agents and direct trauma.

Here are a few of the problems and diseases that can result:

• Structural molecular problems. These include prions (infectious misfolded proteins) such as those that cause Mad Cow's Disease and denaturation of other proteins due to chemical exposures.
• Enzyme function problems. These can include overactivity/underactivity of enzymes, the blocking of enzymatic pathways or a complete absence of particular enzymes altogether.
• Cell signalling problems. These include neurochemical uptake issues (as is possibly the case for many kinds of mental illness) and hormonal imbalance (as in the case for gigantism and dwarfism).
• Cell membrane transport problems. These are involved in cystic fibrosis, as I shall discuss later.

Describe the molecular causes of several example diseases.

Malaria

Malaria is caused by a parasite that infects mosquitoes. Mosquitoes can then pass the parasites onto us when they bite us. The parasites enter our liver cells and reproduce, making liver cells burst. They also infect red blood cells, making them eventually pop. Hence some very severe consequences can often result from malaria, such as weakness, anaemia and death. Malaria is a serious disease, which is why the 2015 Nobel Prize in Physiology or Medicine was awarded to Tu Youyou, who discovered Artemisinin, currently the most effective drug for treating malaria.

So what actually happens within red blood cells to make them pop? Well, once inside red blood cells, the parasites start making lots of changes to make themselves at home. They form small organelles called Maurer's clefts, which fuse to the membrane. They then activate secretory pathways and modify the membrane in several different ways. One of these modifications is the insertion of channels, which increases the permeability of the membrane to various substances, which in turn also increases the rate of lysis.

Cystic Fibrosis

Cystic fibrosis is a disease with genetic origins. It involves a mutation in the CFTR gene, which codes for Cl- pumps in the cell membrane. Since less Cl- can exit the membrane, less water follows by osmosis, and so the mucus that lines body cavities becomes thicker than usual. This can have further implications, such as being unable to breathe properly due to thick mucus in the lungs.

Mind you, overactive Cl- pumps are an issue as well. When too much water is lost, death can easily result from dehydration. It has been suggested that people with one allele for cystic fibrosis may be less at risk for death due to diarrhoea and dehydration in diseases such as cholera.

Muscular Dystrophy

Muscular dystrophies are diseases in which the muscle cells are fragile and therefore more likely to rupture and die. I have some pictures of muscle cells from both healthy and mdx mice (mdx mice are basically mice with muscular dystrophy, used for studying the disease) on an earlier post about muscles.

One fatal type of muscular dystrophy is Duchenne muscular dystrophy (DMD). It's an X-linked disease, so guys are more likely to have it than girls. It is thought that 30% of cases result from spontaneous mutations. Muscles get progressively weaker, to the point where death results from heart or respiratory muscles becoming too weak to support the patient. In Duchenne muscular dystrophy, a protein called dystrophin is missing completely. Dystrophin is a cytoskeletal protein that attaches actin to the plasma membrane. Without dystrophin, there is an increased susceptibility to muscle damage and impaired healing after damage.

Not all muscular dystrophies are fatal, however. (Okay, well, everyone's going to die eventually, but you know what I mean.) Becker muscular dystrophy (BMD) is a much milder form of muscular dystrophy that is not usually fatal. In BMD, dystrophin is present, albeit much shorter than normal, allowing for at least partial function.