Monday, June 27, 2005

Today is a Good Day for SCIENCE!

It's been far too long since I posted last and I've been putting it off like an idiot. I've gotten into a lab here at UTSouthwestern with Dr. David Karp in immunology/ rheumatology. I'm going to give everyone a run-down on my project, in the best terms I can, so everyone can understand me.

You have a type of White Blood Cell called a Macrophage, or MP. These guys eat and kill things that are bad in the body. When certain cells get old, or don't express the right markers, your body kills those bits of itself (all your cells will be new after 7 years) by an action of compact, safe death called apoptosis. Well, many cells in your body, Macrophages included, produce things to keep themselves alive, because your body needs them there. Macrophages produce a small secreted protein called "Apotosis Inhibitor expressed in Macrophages" or simply AIM.

There are cells in your body, called B cells (B stands for Bursar or Bone Marrow -where they are born) which have the job of making Antibodies, the shorthand of which is Ab. Now, Ab is a special protein which looks like a "Y" The arms of the Y are called Fab regions and the body of the Y is called the Fc region. The tips of the Fab regions are really special because they see foreign objects very well. Each Ab is different and all your Abs combined can see over 10,000,000,000,000 different things (that's a lot). Imagine each Y as a lock looking for it's key. The Fc part of the Y can be seen by cells like Macrophages or other White Blood Cells to come eat and kill this thing that is not you. There are 5 types (called isotypes) of Ab in the human model. The Y molecules, although we call them Antibodies are of a class of proteins called Immunoglobulins or simply, Ig. The five types are IgA, IgD, IgE, IgG, and IgM. IgA is found in secretions like mucus, spit, or breast milk. You secrete these IgA to stop bad things (called Antigens, or Ag) before they reach the cells. IgA is secreted from B cells either alone or in a form that looks like two Y's back to back with arms flailing. We have no Idea what IgD does, after 50 years of knowing about it, but it's really not important for anything. IgE is the Antibody that marks worms or fungus for your body to kill them or will also cause cells called Mast Cells to dump histamine and that is why you have allergic reactions to some things. IgG is the most solid of locks, it has a very tight specificity for it's key and can actually cross the placenta from mother and embryo. D, E and G are only secreted in singles. IgM is the least specific lock, but it accepts the most keys and holds them in. IgM is secreted first and then the body will normally switch to IgG. IgM has the amazing ability to be secreted not as a single protein, but in a pentamer. Imagine 5 Y's linked by their bodies with arms flailing in a 10 pointed star! The Y's are held together by a small protein called the J chain.

We never knew about AIM because we only recently (1999) found it stuck to the J chain. The pent. IgM is so large, no one ever saw the little AIM protein in it's mass. Not much is know about how AIM works other than to keep MP alive longer, but we believe that AIM may substitute for the J chain in certain situations. This is where I come in. I am currently building a virus. I'm using a retrovirus (the most famous retrovirus is HIV) to infect B cells. I'm using a hollowed-out HIV virus called a Lentivirus to infect the cells. Before anyone gets all wiggy- the Lentivirus construct is safe. It has been completely gutted, none of the virus remains, it cannot replicate itself inside a cell, and it pretty much harmless. Retroviruses are special because they contain an amazing protein called reverse transcriptase which has the ability to inject viral DNA right into your DNA and become part of you on the molecular level. Well, instead of inserting viral DNA like they normally do, I have replaced the virus DNA with the human gene which codes for the AIM protein. I'll take the new virus and give it to B cells which don't have the ability to make the 5 member form of IgM and if they use the AIM and then suddenly begin to produce the pentamer form, then I've just made a HUGE breakthrough in immunology and I'll probably get my name on a paper.

So that's what I'm doing with my summer project. Post a comment if you got it all or want me to explain something else!


Language is a virus from outer space

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