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sialic acid

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    glycobiology, engineering

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  1. Yes, evolution and the way we understand life needs a complete overhaul. Genetics may be the blueprint of life, but it does not directly encode and contain information about how entire metabolic and proteomic networks interact together to regulate life. Genomics misses a higher level of systems biology that defines life. Darwinian evolution and classic thoughts about genetics and evolution have some very, very profound questions that are difficult to answer. For example, if it takes a mutation and at least one generation for this mutation to be passed down, how then can humans defend themselves against most infections from bacteria and other pathogens if pathogens can replicate by the billions in only a matter of a few hours? Additionally, many mutations would lead to a loss of function for proteins which would often be deleterious, so evolution on the genetic level can not explain how we are still alive today even under the constant bombardment of pathogenic assaults. We'd be wiped out in a matter of no time because evolution from pathogenic stresses would cause many deleterious mutations over time and human genetic evolution is extraordinarily slow while pathogens can replicate orders of magnitude faster. There's obviously a higher level of control outside the realm of genetics that allows human to adapt to environmental stress that also regulates many aspects of life. Our view of life is overly reductionist and the reason why genetics has failed to produce the ground breaking cures promised is because we have long ignored those mechanisms outside of genetics which regulate life at the systems level. Forever now we've ignored many other -omics fields and one of the biggest ones we've ignored until about the end of the 20th century is the role that carbohydrates play as another essential macromolecule that truly defines life. Carbohydrates and glycomics are called now called the "3rd alphabet of life" after DNA and proteins. The DNA code and proteome is surprisingly quite small in contrast to the glycome--- the total sum of all carbohydrate structures that get added to proteins post translationally. The glycome is orders of magnitude more complex than the proteome or genome and is possibly one of the most complex entities in nature. The glycome takes proteins and completely alters their behavior ( even though the proteins have the same exact sequence) or can fine tune their activity. The same protein in different tissues or areas within the same tissue can behave differently-- and it is due to multiple glycoforms of the same protein. Carbohydrates can dominate biology, and its why glycobiology and glycomics are predicted to revolutionize medicine in the next 100 years. Almost every single aspect of the immune system is in some way regulated by carbohydrates and the glycome. Life requires fidelity AND flexibility. While DNA and proteins provide fidelity and make up the cornerstone of Darwinian evolution theories, classical evolution arguments based on DNA absolutely fail to explain many important phenomena regarding evolution, such as the example above, where we somehow have the bility to survive under constant assault from pathogens without the need for high speed genomic mutations and evolution. This is where flexibility of the human genome must come in, and this flexibility is controlled through both glycosylation and epigenetics. The glycome can be rapidly altered in response to environmental cues and stresses to significantly change the physiological function of the genome and proteome. Changes in glycosylation to modulate our immune system and fight infection allow us to survive while simulataneously allowing us to avoid mutations to our proteins that would often be deleterious and would probably cause important proteins to become inactive. DNA and proteins would be equivalent to Newtownian/classical physics while sugars and glycomics are now being viewed as basically the "quantum physics" of biology--there's simply no code to controlling the glycome, it responds in a stochastic manner, but it is significantly perturbed in many diseases and altered in ways we do understand to unlock different physiological functions of the same protein to ultimately produce a massively expanded landscape for the physiological possibilities of all proteins encoded by the genome. In much as the same way a ton of physics could not be explained until the advent of quantum/non-classical physics, tons and tons of biology can not be explained by the genetic code, classical views of Darwinism, and proteins. What lies outside of the realm of the genome and genes, such as the glycome (which is orders of magnitude more complex than the proteome), is a massive missing piece of the puzzle for understanding life and evolution at the systems level and alterations to the entire glycome, which can occur due to epigentics and metabolic abberrations, can profoundly alter the entire physiology of a cell through alteration of the glycome. Even more strikingly, new studies are beginning to show that sugar patterns from parent to offspring can even be passed down from generation to generation and gene expression alone isn't enough to explain how those sugar patterns can be passed down.
  2. Yup, GMOs are the answer. http://www.nature.com/ncomms/2013/131217/ncomms3918/full/ncomms3918.html As always the REAL truth lies somewhere in the middle.
  3. This thread makes no sense. How is knowing the existence of a god particle or quantum mechanics going to help you do a 10 step synthesis to create a new drug? You can have all the QM you want, it will barely help you do synthetic organic chemistry. You can't even solve the time dependent schrodinger equation for a 3 bodied problem. How am I supposed to use QM to help me perform multistep procedures? I love to always read the claim that everything reduces to physics. We used to run the most advanced quantum computing software available at the time to perform virtually screening of compounds against our desired targets. What was hilarious was that when we actually synthesized the compounds and tested them in real life against the target, often times the compounds that were "supposed to be" the best compound against the target were often the worst, and what were supposed to be the worst compounds against the target often ended up being the most potent. It just shows you how unpreditable nature can be, even if you have a working model of quantum theory. If you actually read the fine details of many models of physical systems, they often include ridiculous assumptions that often fail apart in the real world. Many complex examples biological phenomena described by physics often assume things like steady state systems to make the calculations and modeling easier. In the real world however, SS almost never exists in many important scenarios.
  4. I haven't looked into any of the details, but a quick google search shows that people have done HPLC analysis on the compound. HPLC would be a fantastic and pretty reliable way to do it. Interfering proteins or not. The free form absorbs at 226 nm, so it may be a little bit of a challenge with regards to your mobile phase to make sure something wouldn't absorb there too and to get a good signal since it is a low wavelength and noise may be an issue. I have however done simple UV absorbance of carbohydrates that have poor UV absorbance and had to use 210 nm. It still worked. If you chelate it with Fe(3+), the iron bound form can absorb at 430 nm which may make it easier if you have to use an organic solvent system.
  5. In the future, I expect that better antibiotic agents won't necessarily have the primary goal of killing an infectious disease, but rather change the way it can interact with the extracellular enviroment,, manipulate, bacterial adhesion, quorum sensing, etc.
  6. You still have to show that injection right into the tumor will be better or provide added benefit compared to what can be done surgically or with radiation. Many tumors can be removed with techniques and technology we already have, it's the metastases however that kill you, which of course will be very hard to contain without systemically administering something... With regards to drug delivery technology, no one wants to point out the elephant in the room, but one of the biggest hindrances to drug delivery technology is the technology itself. Whenever you package something into a delivery device it is considered to be a new entity by the FDA and all clinical trials must start over from scratch again. Often times, however, delivery devices are developed separately from new small molecules and biologics designed to be new drugs. If I'm a drug manufacturer that just spent $100 million to get my drug through clinical trials to show safety, why would I use a drug delivery device if I had to start all over again from phase I? Many times companies that develop new drugs simply aren't willing to partner with drug delivery technology owned by another company in the early phases of trying to get a new drug approved either. IP and regulatory roadblocks are a major major problem in the realm of drug delivery. Yes you can find a few fleeting examples of drug delivery technology that is being used, but for all of the money we've dumped into it, the returns are quite underwhelming IMO. The #1 way to create a new drug is still to improve the chemical design of your small molecule and give it directly to a patient rather than using some complicated delivery system that is clouded with IP and regulatory issues.
  7. I'm still on the fence about GMOs. Sure they promise to feed the world, but at what cost? Who gets the patent and how much will they control? Additionally, what often gets overlooked is the fact that relying on GMO use often creates practices of monoculture or very limited diversity in our food chain. Who wants the same old boring and tasteless 2 tomatoes? What often gets lost are the hundreds and thousands of heirloom varieties of almost every type of produce and livestock known to man. And that comes at the cost of flavor. A tomato is not just a tomato, corn is not just corn, and wheat not just wheat. Different breeds of tomatoes produce radically different flavors and textures. As a consumer, I also have the concern that GMOs also run the risk of pigeonholing the availability of choice you have when it comes to the spectrum of flavor that will be available in food. Food and food flavors strongly reflect the way that they're grown and the life they've lived. Ask almost any chef the difference in the taste of meat between something like a factory farmed hog and a Spanish Iberian pig. What often gets lost in allllllllllll of the science are the flavors nature has imparted into our food through millions of years of evolution and flavors humans have introduced through millenia of farming practices. All of the sudden corps like Monsanto et al. know how to farm better than what humans have learned through thousands of years of practice? Also, for all of the promises GMOs offer, do you really think major corporations are going to give away their technology for free? Of course not. GMO crops won't be feeding poor countries or the starving since they won't be able to afford GMOs in the first place. Even if those countries somehow are able to get GMO crops, it'll just reinforce poor countries' dependency on richer nations every single year.
  8. Which comes first, the chicken or the egg? I'm still a firm believer in Warburg's initial hypothesis that metabolic alteration is one of the primary drivers of genetic mutation (not the other way around, but of course that's debatable) which eventually leads to cancer tumors with heterogeneities, stem cell like characteristics, and the ability to metastasize. Either way, energy metabolism, at least IMO still remains a very viable target for cancer therapy that will be very hard for a cancer cell to become resistant to if you know where to target.
  9. Congratulations, you made all of the parts, now what? Life is much more complicated than the sum of its parts (DNA + proteins + membrane + golgi + etc. etc does not equate to a cell), cell physiology is much harder to understand and play around with than anatomy. Just because you put all the pieces a cell is made out of together doesn't mean you'll get a properly functioning cell. Cells respond to spacial and temporal cues with extremely complex signaling networks, how do you hope to control something like simple like energy metabolism just by putting the pieces of a cell together? You solved energy metabolism eh? How about the rest: http://web.expasy.org/cgi-bin/pathways/show_thumbnails.pl http://web.expasy.org/cgi-bin/pathways/show_thumbnails.pl?2
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