Antibody Diversity

Why are antibodies so diverse? This is a question that I found quite challenging on the assessment exam since I have not taken an immunology course. Although I know the background on how an immune response works and I use antibodies for research purposes, I have never learned how antibodies become so diverse. Humans can produce 10¹² different antibodies, but how is this genetically possible when there are not enough genes in the genome to code for that many different antibodies?

Interestingly, all antibodies contain a light and heavy chain; however, the area that makes antibodies so diverse is the antibody binding site. As you can see in the picture there is a variable region in the antibody binding site on the light and heavy chain; these changes are necessary on both chains because a lock and key fit is needed for the antigen to bind to the antibody. This distinct binding site of the antigen is called an epitope; the antibody recognizes this specific site and then binds to it producing the immune response. For research purposes we use antibodies to bind to epitopes of specific proteins, in Western Blotting, and have a secondary antibody bound that has a fluorescent tag; this enables easier detection. Let’s get back to the original question, the genetic event that makes antibodies diverse is DNA rearrangements followed by alternative splicing of the transcripts; this allows humans to produce a million different antibody molecules with a limited genome code. On human chromosome 14 a heavy chain variable domain can be found and on human chromosome 2 and 22 a light chain variable domain can be found. The variable domain is where the DNA rearrangements occur. The domain regions are actually more complicated than that, but this is just a basic description.

Antibodies are a topic of study within themselves, but should a person necessarily know this information. I believe having a basic understanding about an immune response and how binding is a lock and key fit with the antibody and antigen epitope is necessary. Since not all biology students take immunology I think it would be good to talk about this in genetics class, since it would be useful for medical school. There have been many research studies to better understand the diversity of antibodies for molecular assays, for learning about the evolution of antibodies, and for disease understanding along with possible therapies.

For basic information about antibody diversity i read this abstract and introduction since that was all that was available without purchasing. http://www.ncbi.nlm.nih.gov/pubmed/21310488

I also read this research review article called: Antibody Structure, Instability, and Formulation written by Wang et. al., which i found at the AU electron journal center.

Master of Disguise; The Sea Urchin

Have you ever gone somewhere not wanting to see anyone you know, and instead you end up running into EVERYONE you know? Often at these times we think of how wonderful it would be to become invisible, but from now on I am going to think of how wonderful it would be to become a sea urchin. Sea urchins are marine animals that belong to the phylum echinoderms.

This is the same phylum that includes sea stars, sea cucumbers, and brittle stars. A characteristic of echinoderms is their pentamerism radial symmetry. Pentamerism radial symmetry is a division of the body into five parts. The internal organs of sea urchins are surrounded by a skeleton, called a test. The test is made out of calcium carbonate and divides the sea urchin body into the five ambulacra and inter-ambulacral areas. Each of the five ambulacra and inter-ambulacral areas contain two rows of plates. Tubercles cover each plate, in which the infamous spines of the urchin are attached.

Another characteristic that sea urchins have, along with other echinoderms is a water vascular system. The water vascular system is a hydraulic system that functions in locomotion, respiration, and food and waste transportation. An essential part of the water vascular system that aids in locomotion are tube feet. The tube feet allow the sea urchin to move and/or attach to surfaces in the ocean. While the tube feet aid in locomotion, they can also aid in camouflage. Sea urchins are able to hide from their predators by using their tube feet to pick up parts of their surroundings, such as seaweed and small rocks. They then cover their bodies in these objects and are able to blend in with their surroundings thus evading their predators.

Oh, what I would give to be able to blend in with my surroundings, just like sea urchins, in order to evade the people that I know when running my errands. It definitely sounds better than trying to hide in a clothes rack, or finding a distant aisle to hide in.

Biglycan to the Rescue!!

Walking across campus, raising your hand in class, and even typing on a keyboard are all actions which we complete on a daily basis without much thought. However, each is quite complex on the cellular level and, among other processes, requires your muscles to contract. Luckily, such action is automatic, and we don't have to tell ourselves to release say, actylcholine at a neuromuscular junction every time we move a muscle. However, with this innate response we often tend to forget how lucky we are to perform such simple actions. Unfortunately, some individuals do not have this gift. Those diagnosed with Muscular Dystrophy have weak muscles due to insufficient proteins and are unable to complete such actions previously listed. Sadly there is no known treatment for this disease, until now....

An article published by Science Daily in December 2010 described a novel treatment which may save those diagnosed with Duchenne Muscular Dystrophy. Individuals with this disease are unable to produce dystrophin (a crucial protein which keeps muscle cells strong). Early symptoms, include by the age of eight they are unable to walk, and generally do not live past their 20's. The solutions to this protein deficiency is to supply the body with biglycan (another protein) which restores the key protein utrophin which strengthens muscles. Utrophin is usually only found in children. Although low levels are present in adults there is not a high enough concentration to prevent the adverse affects of Muscular Dystrophy. When biglycan is added to the patients bloodstream, utrophin is drawn out from muscle cell membranes. Once, activated by the presence of biglycan, the protein utrophin then helps rebuild and maintain cellular strength.

Although humans have not been tested, initial laboratory experiments revealed 50% less of the cells treated with biglycan were damaged from stress tests, indicating they were indeed stronger. The image depicts cells treated with biglycan (bottom) vs. the absence of biglycan (top). Hopefully this method will prove to be effective to humans and provide a solution to this disease.

Understanding Gene Flow may be crucial to our future

Migration is one important factor affecting the genetics of a given population. Migration of one species to a genetically different population allows for gene flow between the two species. Gene Flow is different than Natural Selection and Genetic Drift. Genetic drift can lead to the existence of completely separate subpopulations (genetically). Migration and gene flow can oppose these effects because it tends to make sub-populations more homogeneous. So basically, gene flow does not increase the genetic variability between the migrating and receiving populations, it does the opposite. Gene flow makes two populations more similar. So why is this important for a biologist to know?
   Gene flow is a concern for many of us, whether we know it or not.  Many scientists have been working to better understand gene flow from genetically modified plants to the environment. Genetically modified food may have a negative impact on humans as well as the environment. Environmental concerns include; use of pesticides, pesticide resistance, gene transfer to non-target species, and harm to other organisms. For example, pollen from genetically modified corn was found to increase mortality rates in Monarch Butterflies (from a nature article (1999) cited in hyper-linked article).
   Understanding gene flow is not only important in the food industry, but also to the conservation of many different species. For instance, Scientists from the Chinese Academy of Sciences found that understanding how environment affects gene flow can be important to conserving Giant Pandas. Fuwen Wei said "These results suggest that gene flow will be enhanced if the connectivity between the currently fragmented bamboo forests is increased. This may be of importance to conservation efforts as gene flow is one of the most important factors for maintaining genetic diversity within a species and counteracting the negative effects of habitat fragmentation."
   So as you can see, understanding gene flow and it's consequences is important for any scientist, especially those dealing with conservation and environmental issues. However, I feel that in our time, every person, whether knowledgeable about science or not, could benefit from understanding gene flow because genetic experimentation is very popular and influences many people.

Infecting our Primate Neighbors

Gorillas share up to 98% of their DNA with Humans. While these genetic similarities have always created feelings of curiosity in us, it potentially poses a great threat to this fragile species. It has been assumed for years that because of our close genetic relationship with Gorillas, that many diseases could pass between our two species. Because of the fact that the Mountain Gorilla population has dwindled down to approximately 800 members, protection from humans has always been a crucial goal.

It has long since been assumed that by creating wildlife preserves for these great mammals, much of the danger from the human population would be taken care of. However, most of the preserves located in Rwanda, Uganda, and The Democratic Republic of Congo are found in the most heavily populated area of continental Africa. It goes almost without saying that the more people that can be found in one place, the more diseases can be found also. Gorilla tourism has also added to the problem of human contact. While in many ways this tourism has allowed for a greater understanding for the need for Gorilla protection, it has also exposed them on a near daily basis to human diseases. It has recently been determined that the Human Metapneumonovirus (HMPV) is the second highest cause of Mountain Gorilla death in the last few years.

HMPV is an RNA virus, which causes respiratory upset in both Humans and in Gorillas. The symptoms range from a simple cold all the way up to severe pneumonia. These symptoms have been documented in the Gorilla population for some time, but the direct correlation was not determined until the death of an adult female and an infant in 2009. Both of these animals were discovered to have clear signs of HMPV, and it was determined to be the cause of death. These findings have uncovered a new set of dangers facing this fragile population. While the solution to this serious problem has yet to be determined, researchers are following these Gorillas even more closely in the hopes of preventing the further spread of this disease.

Wendy and Rachael Audio Project

Wendy and Rachael Interview Dr. Fenster

Melissa, Katie, and Rachel's Audio Project!

http://dl.dropbox.com/u/459618/495%20audio%20projects/Katie%20Melissa%20and%20Rachel.mp3