Future Research

Hello,

I don’t have any new results to share from my currentexperiments so I thought I would share a flashy picture and explain what workis in the pipeline.

 

This is an image of a section of Nothobranchius guentherioptic nerve (this is unpublished work so I can’t go into much detail here). Theoptic nerve has been stained with Tomato lectin and an L-plastin antibody. Thegreen is the tomato lectin that is supposed to label immune cells (it seemslabel a lot of other stuff too, which is a problem). (The blue are cell nuclei.) The red is L-plastinprotein labeled with the anti-body. These are immune cells but perhaps not allthe immune cells that are actually present---L-plastin is supposed to be a general marker of immune cells in fish. The Tomato lectin does label immune-like cells (the bright green blobs and donuts) that theanti-L-plastin doesn’t. So something interesting is going on here…

The plan, for the future, is to generate antibodies that arespecific to the Nothobranchius immune cells. There are two types I am mostinterested in: macrophages/microglia and neutrophils. The latter seem to playan important part in optic nerve regeneration and other wound healing processes(http://www.ncbi.nlm.nih.gov/pubmed/24453300). If they don’t move into thewound area then the macrophages don’t follow and do their job properly. We knowthat a certain protein, ITGAM is increased in aged fish (http://www.ncbi.nlm.nih.gov/pubmed/23496936).This is a marker of macrophages. So this is one of the proteins I want to makeantibodies to. MPX is a marker of fish neutrophils (http://www.ncbi.nlm.nih.gov/pubmed/18182572). I am also interested in Lymphocytes (these are the cells responsible for adaptive immunity and the generation of antibodies). Lymphocyte specific markers haven’t been identified but the proteins Rag2, Rag2 and IGHM look promising.

With age, macrophages in mammals tend to get stuck in the “on”position in the brain and then cause problems. These cells increase the expression of ITGAMand AIF1 (one of the antibodies I would like to buy if we exceed the campaigngoal). This is also a good marker of brain inflammation and is reasonablyspecific for microglia (the immune cells of the brain). As well as gettingstuck in the “on” position there is also a loss of immune cells with age. So,if my anti-aging treatments work, is there a decrease in pathologicalinflammation (macrophages stuck in the “on” position), a restoration of immunecell numbers or both? We know from parabiosis experiments (when a young animalis joined via their blood to an old animal) that there is somethingrejuvenating in the blood (http://www.ncbi.nlm.nih.gov/pubmed/24812376). At thesame time, we know from other experiments that the preservation of the brainseems to extend lifespan and improve immunity all at once (http://www.ncbi.nlm.nih.gov/pubmed/11021802, http://www.ncbi.nlm.nih.gov/pubmed/12817143 it was this latter paper that really got me interested in aging research!). So what is going on?We know that Nothobranchius fish also have a loss of immune cells with age (http://getquest.com/msucvm/images/pdfs/Student%20Abstracts%202012.pdf).

Alessia is working with neuropeptide Y. This is a hormonethat signals the need to eat (yes, as the fish get old they have eatingproblems…) but it is also an immune system modulator. Is it a link between theimmune and nervous systems? Over expression of neuropeptide Y is linked with aloss of natural killer cell activity (that kill cancer and virus infectedcells) in the aged and stressed (http://www.ncbi.nlm.nih.gov/pubmed/1743441).So what is going on there? We don’t know. There other hormones as well, such asmelatonin that modulate the immune system but melatonin supplements haven’tstopped aging in people… But I still need to give some too my fish and see whatit does… (There is work showing that melatonin corrects for someaging-associated behavioral problems in Nothobranchius, http://www.ncbi.nlm.nih.gov/pubmed/23466303)

We have a model system to assess both aging-related tissuedegeneration and immune system; as well as tissue regeneration, and now forinfection as well (http://www.ncbi.nlm.nih.gov/pubmed/25141004, http://www.ncbi.nlm.nih.gov/pubmed/9878725 *). All of this can be tested in our little fish.

*These experiments sound cruel but having tried these, the moment the anesthetic has worn off the fish go about their business as usual, even trying to spawn. They don't exhibit any discomfort---much to my surprise & relief!