Justin's Microbiology Journal
Monday, May 24, 2004
Ebola seems to be in the news a lot lately. A Russian scientist just died from a needle prick in a lab, and a new strain of Ebola seems to be responsible for the illnesses seen in Sudan. I also noticed that an America post-doc grazed her finger and survived an attenuated strain, although she had to spend time in the Slammer.
I found the analog to the CDC worldwide, PROMED, the program for monitoring emerging infectious diseases and toxins.
Right now I'm studying clinical microbiology and immunology. It includes growth dependent clinical identification methods, immunology and diagnostics, and molecular and visual methods. I finally learned how the blood type classification of A,B, AB, and O and Rh factor work molecularly as antigens expressed on red blood cells.
Friday, May 21, 2004
To follow up on the viral hemmorrhagic fever post, a new ebola like outbreak has been reported in southern Sudan. Here's a post with more information, no word yet on whether it's different from Ebola or a variant of it. Here's the WHO page.
Hard at work studying the immune system. I've got to say this is some of the harder biology for me to understand so far.
Last few days I've covered immune response, antigens, T Cells, cellular immunity, antibodies, immunization, and immune response diseases.
Right now I'm working more specifically on molecular immunology. Looking at the details of the immunoglobin gene superfamily, major histocompatibility complex cellular membrane proteins, antibody proteins and antigen binding, TCR proteins and genes, and molecular signals in immunity.
I've also started a rough draft of my resume. Since I haven't written one for 9+ years, I'm not sure what I need to say. I think I can leave off anything more than 15 or so years old.
I'm also a bit sick right now, probably a rhinovirus from Elena, who's had a runny nose, sore throat recently. Going through the first stages where the virus is causing minor rhinitis, general malaise, and sore throat.
Rhinoviruses are single stranded RNA viruses in the picornavirus group, although other viruses cause colds as well. Coronaviruses (like the SARS family) cause about 15% of colds, adenoviruses, coxsackie viruses, respiratory synctial viruses and orthomyxoviruses cause a total of around 10%.
We really don't have any effective antiviral drugs, although work is ongoing. One such drug is called WIN 52084 binds to the virus surface and disrupts the cellular binding site.
Sunday, May 16, 2004
Finished reading The Hot Zone, about Ebola and other filoviridae hemorrhagic virii. A good read, and a good reason why I want to get into biology research. There's lots of knowledge out there, and lots of conflicting memes in the world, so work is needed on getting all bioterror weapons effective vaccines, supportive treatment options, and quicker detection techniques. Seems as of 2003, I've read one report that a virus has been shown effective in monkeys. Pravda also reported 4 days ago a new vaccine developed by Russian scientists. Not sure how accurate that is even though I got the link off Google news.
The last outbreak of Ebola was in January 2004 in Mbomo in the Republic of the Congo, with 35 cases, and 29 deaths.
Right now there are 3 major disease outbreaks going on in the world: Dengue Fever in Indonesia, Yellow Fever in Burkina Faso, and SARS in China. Here's a page from the WHO that lists all disease outbreaks going on in the world. Disease Outbreaks.
Out here in California, the biggest occurring viral concern is probably hantavirus, which has a mortality rate of 40-50%, but is still quite rare.
Thursday, May 13, 2004
My microtome came in the mail today. I should now be able to create 10 micron thin sections of various tissue cultures (plants mostly) and work on my staining techniques. Look for some pictures tomorrow or the next day. Of course, my first attempts may end up a complete disaster, I've never used paraffin, microtomes, or some of the stains I'm going to try.
I'm currently studying human immunology. Large topic, so it should occupy my time for the few days.
Wednesday, May 12, 2004
OK, so here is my post on chemotherapeutic agents for microbe control. Some substances which inhibit microbial growth that occur in nature as part of another organisms defense mechanism we call antibiotics. Those which are purely synthetic compounds we call synthetic agents. The line between the two has blurred, since through our understanding of antibiotic chemical structure, we've been able to produce semi-synthetic antibiotics. Both differ from disinfectants and antiseptics in that they must kill bacteria within the body of the patient without causing undue damage to the patient.
Growth Factor analogs are substances structurally related to bacterial growth factors, but the difference is such that they cannot be used for the same function as the original growth factor. The first growth factor analog were the sulfa drugs, the simplest being sulfanilamide. Sulfanilamide is an analog to para-amino benzoic acid, which is part of folic acid, which is used as a nucleic acid precursor. Higher animals get their folic acid from external sources, bacteria generate their own, which is why sulfanilamide blocks bacterial growth but not higher animals. Trimethroprim also acts on folic acid metabolism.
Other synthetic compounds called quinolones block bacterial DNA gyrase from packaging bacterial DNA. Eukaryotes have chromosomes and use a different packing mechanism from prokaryotes. Some of the more famous quinolones are ciprofloxacin and norfloxacin. Quinolones work on all forms of bacteria, gram positive and gram negative, and are the drug of choice against anthrax and urinary tract infections.
Antibiotics that block protein synthesis by interacting with the bacterial ribosome include streptomycin, tetracycline, chloramphenicol, and cycloheximide. Tetracycline inhibits the protein elongation from the ribosome, while streptomycin inhibits the protein chain initiation. One of the issues with interfering with prokaryotic protein synthesis is that our own mitochondria use the same mechanisms and can be affected by high doses of the drugs in question.
Some antibiotics target RNA synthesis, such as streptovaricins and rifamycins by attacking the beta subunit of RNA polymerase. Actinomycin combines with DNA and prevents RNA synthesis.
Many antibiotics target the structures of the bacteria themselves, the most famous being penicillin like antibiotics called beta-lactams. Some beta-lactams like cephalosporins and penicillins target bacterial cell wall synthesis, notably the cross-linking of glycan linked peptide chains in the cell wall. Transpeptidases perform this linking, and the antibiotics bind to the transpeptidases, resulting in a weakened cell wall. This eventually leads to cell lysis. Vancomycin blocks the transpeptidase reaction by binding to the peptidoglycan precursor. These are generally very low toxicity, effective antibiotics, but some people do develop severe allergies to some of the compounds.
Streptomycin, neomycin, and others inhibit protein synthesis at the 30s subunit of the ribosome. These are known as the aminoglycoside antibiotics, but are not used as frequently anymore because of bacterial resistance and some large side-effects, such as toxicity to kidneys and balance problems.
Tetracyclines also inhibit protein synthesis at the 30s ribosomal unit. One of the values of the chemical structure of tetracycline is that there are 4 different substitution sites that allow for differing chemical analogs, some of which act in unknown ways but can actually cause bacterial cell lysis.
Erythromycin belongs to the family of antibiotics called macrolides. It inhibits protein synthesis at the 50s ribosomal subunit, and is very useful for people who have allergies to beta-lactam antibiotics like penicillin.
Polymyxins, imidazoles, polyenes and other antibiotics target the cytoplasmic membrane and alter it to make it leaky, diffusing the required cellular metabolic compounds. Polymyxins target bacterial cytoplasmic membranes and polyenes target fungal cell membranes.
The reason virii are so hard to treat compared to bacteria is that they use more of the animals existing replication, synthesis, and metabolic machinery instead of their own. This means fewer targets to disrupt, since disrupting those areas would mean you are disrupting the higher organisms own normal metabolic and catabolic processes.
Tuesday, May 11, 2004
Just a quick post. I've had a great burst of studying microbial interactions with humans, both positive and negative, and of studying various techniques for controlling and killing microbes.
Finally I understand chemically the various antiseptics, disinfectants, growth control factors, and antibiotic actions and effects. Knowing by what pathway how growth control factors and antibiotics work and are classified is so useful, I should summarize it and post in a separate blog.
I also want to stress the value of probiotics. We absolutely depend upon a healthy flora on our skin, in our gastrointestinal (and for women vaginal) tract, and in our nasal and upper bronchial mucus. For example, many people only get sufficient vitamin K from the metabolic byproducts of bacteria in the intestine. Especially when on various broad spectrum antibiotics, we not only kill pathogenic bacteria, but essential bacteria as well. This can lead to opportunistic infection by pathogenic bacteria, vitamin deficiencies, and understimulation of the immune system.
Lactobacillus bulgaricus and Streptotoccus thermophilus are found in live yogurt cultures, but do not live past the stomach. So other species of bacteria should be used, like Bacillus Subtillis found in natto (fermented soybeans), lactobacillus casei strain shirota found in a Japanese drink called Yakult, and preparations of enterococcus and escherichia coli in pill form, all of which should survive into the intestine.
Saturday, May 08, 2004
There's a neat site that allows you to search for any chemical based on formula, partial name, CAS number, or weight. It's called chemfinder, and I'm using it to look up various biochemical compounds I come across in study.
My molecular model kit and my organic chemistry book came in. I'm using Organic Chemistry by L. G. Wade, Jr. This is the area I need the most study in, since my background is lacking. I'm probably going to start interspersing my microbiology with my ochem studies.
Elena is having a fun time making the molecule models. She already knows what water looks like, and O2, carbon dioxide, and octane. She can even count the number of hydrogen versus carbon atoms for alkanes. However, her favorite activity is using cyclopentane as a princess crown :)
Almost done with my microbial interactions section.
Wednesday, May 05, 2004
I'm coming up on my one year leave from a full time job. It's time to start applying myself towards a job search while I decide which area I want to continue research into. I'll probably look at short term contract software development jobs to give me the freedom to continue research. Already found quite a few development job postings for biotech companies, that's probably the way I'll get my feet wet to see if the lab environment is appealing.
All done studying methods in microbial ecology: enrichment and isolation of cultures, viability and quantification via staining including fluorescent in-situ hybridization, genetic stains, radioisotopes and stable isotope usage.
Also finished microbial habitats, including soil, fresh water, marine, deep sea, hydrothermal vents. On to interactions with plants and animals including syntrophy, the carbon, nitrogen, sulfur, and iron cycles, and methanogenesis.
After that I get to a fun section on microbial growth control, which I'll probably actually use in day to day life. Learning exactly what sterilization methods work in which ways and on what form of microbes will be useful.
Monday, May 03, 2004
Thought this was a neat application for stem cell research. Then onto regrowing hair for male pattern baldness :)
Growing new teeth.
Just ordered a microtome to cut samples. I'm going to try and veer away from bacteria for a bit and try and stain some eukarykotic tissue samples instead. The tome I got will cut down to 10 micrometers, not great but should be enough for now.
Also finished up studying the metabolic diversity of microorganisms. Nitrogen fixers are my favorite, with their specialized Vanadium/Molbydenum-Iron-Sulfur nitrogenase cofactor. It's one of the only ways free nitrogen in the air can be integrated into organic molecules, as the triple bond of nitrogen requires a lot of energy to overcome. I'm now studying isolating, enriching, and sustaining cultures.
