User:Mausfield

I am an evolutionary biologist interested in human origins, and in particular our unusual sialic acid glycobiology and how it shapes our unique immune systems and life history. On Wikipedia my main project is improving articles related to those topics. For example, there are thousands of Wiki articles on glycoconjugate biomolecules and currently only 197 pages categorized as such!

What is glycobiology? What the heck is a glycoconjugate? Glad you asked ....

LYCOBIOLOGY is the study of the billions (yes, billions) of different combinatorial outcomes that occur when sugars (also called saccharides) are added to biomolecules in a process called glycosylation. The enzymes that do this work are glycosyltransferases (the adders) and glycosidases (the removers). For example: proteins, lipids, and amino groups can be glycosylated to yield glycoproteins, glycolipids, and glycosylamines, respectively. 

The same type of protein may often have different layouts of sugars (or "glycans", once they're involved in this situation) which are called glycoforms, similar to protein isoforms. In mammals, the two major domains of protein-modifying glycans are N-glycans which attach to asparagine residues (in biology a "residue" is just an individual molecule when many of that molecule are involved in something) and O-glycans which attach to serine or threonine residues. N-glycans are a kind of family tree, in that they share a common starting point called the pentasaccharide core, seen below as the bottom two blue blocks (a sugar called N-acetylglucosamine or GlcNAc, pronounced "glook-nack", the funnest word in biology), the first mannose above them, and the two mannose residues above that.

O-glycans have several more starting core structures (and certainly more we have not found yet), and like N-glycans they do all kinds of amazing work in our biology, such as attracting a ton of water to form the mucous in our mucous membranes, providing the starting point for our bones, helping hundreds of our intracellular proteins fold in the right ways, and much more. Wikipedia is an incredible resource for biology around the world, and glyobiology has historically been under-appricated despite its intimate involvement in nearly every biological outcome. My main project on Wikipedia is increasing the recording of established understanding in glycobiology.

Now go join WikiProject: Molecular Biology and help CATEGORIZE!

Even a single sugar can have a huge effect on our biology, such as defining our ABO blood group (see right). If you have a regular galactose on your h-antigen precursor added by your trusty galactosyl transferase, you're in group B. If that galactose has an N-acetyl group on it because you have a fancy N-acetylgalactosaminyl transferase, you're in group A. If you have any of the various mutations that result in neither, you are stuck with the h-antigen precursor are in group O (go donate blood please). About 2–3 million years ago, someone in our lineage experienced a mutation that made them unable to produce a very common vertebrate sugar, a sialic acid called 5-glycolylneuraminic acid or Neu5Gc from its closely related starting material, Neu5Ac. This appears to have had widespread effects on our biology, at the very least making us molecularly invisible to the many pathogens which use Neu5Gc as their hook to get into target cells. Fun fact! The "H" in influenza strains (you've probably heard of H1N1) stands for a sugar-binding protein (also knows as a lectin) called hemagglutinin. The "N" stands for neuraminidase (which is reall a sialidase), and lets influenza virus particles release themselves from the sugar-coated surfaces of our red blood cells by chopping off those same sugars they grabbed to get inside. Variations in these two proteins define the influenza clades we care about in medicine, and have wide-ranging effects on how well a given flu spreads or affects someone who gets it.

So, sugars have a huge presence in the barriers that separate the basic pieces of life, including the different compartments within us and the meeting point between our cells and the massive number of external things they encounter. One of the most evolutionarily important roles they have is in helping organisms distinguish information about the world around us. This may sound trivial, but the self vs non-self problem is a recurrent them in major evolutionary transitions, and we can today see the big problem-solving steps when we compare single- to multicellular organisms, multicellular to multi-tissue organisms (which defines Eumetazoans), and multi-tissue organisms to mammals, who of course had to figure out carrying around a foreign–but tolerable!–little individual for some period of time (go thank a mom somehwere).

Evolutionary transition	How long ago? (in billions of years)	New cellular awareness	New type of "self"	Self-identifying examples
Single cell	3.9 to 4.1	Me vs environment	Chemical self	Lipids and membrane proteins
Lineage of cells	3.5 to 3.8	My genetics vs other genetics	Genetic self	Cell-surface glycoproteins, enzymes recognizing nucleic acid sequences
Eukaryotic life	1.8 to 2.1	My friends vs non-friends	Symbiotic self	Compartments within the cell, membrane trafficking proteins
Sexual reproduction	1.2 to 2	That stranger is hot!	Reproductive self	Mating system, gamete recognition markers, compatibility checks
Multicellular life	0.6 to 2.2 (and onwards)	My neighboring cells vs strangers	Diverse self	Adhesion proteins
Multi-tissue life	0.6 to 0.65	My diverse cell types	Intrapersonal self	Diverse glycocalyx, tissue-specific markers, junction proteins, nerves and endocrine system
Teachable immune system	0.43 to 0.48	My changeable friends and enemies	Teachable self	MHC, T- and B-cell receptors, and adaptive immunity

..WIP....