Stanford Synchrotron Radiation Lightsource

The bacterium Clostridium difficile (often called C. diff) can cause severe intestinal infections, responsible for about 500,000 cases and 29,000 deaths in the United States per year. While infections are more often found in ill and elderly people, infection rates are increasing in young and healthy people. The bacterium makes and secretes two related toxins, TcdA and TcdB. Understanding the structure of these molecules is a critical step to developing treatment. Unfortunately, since these toxin proteins are huge and flexible, scientists have been unable to determine the entire molecular structures until now.

Microtubules (MTs) are sub-cellular structures made of the protein tubulin. They have important roles in moving organelles around the cell and in chromosome segregation before cell division. MTs can exist in two states, either a dynamic state of growing and shrinking MTs or a stable state. MTs can also form complex bundles that can be found in neuronal axons. The neuronal protein Tau helps facilitate this process and has been implicated in some neurodegenerative disorders like Alzheimer’s disease. Yet Tau’s exact role in MT formation and bundling is unclear: different experiments (both in vivo and cell free) have shown Tau to mediate either attractive or repulsive forces between MTs.

Many organisms produce chemicals known as secondary metabolites that are not directly vital for survival but often play important roles in the organisms’ defense against other species. Due to their wide range of medically relevant properties, these compounds are also of great interest to humankind. The secondary metabolite erythromycin, for instance, is an important antibiotic of bacterial origin. Recently, researchers have shed light on the structural architecture of 6-deoxyerythronolide B synthase (DEBS) – a large multi-protein complex that acts as an assembly line for one of erythromycin’s precursors.

Of the 11 species of Neisseria bacteria that colonize humans, 9 of them coexist peacefully with us. However, two can cause serious diseases N. gonorrhoeae, responsible for the sexually transmitted disease gonorrhea, and N. meningitidis, which causes septicemia and meningitis.  Commercially available vaccines exist for four of the five known disease-causing serogroups of N. meningitidis (A, B, C, Y, W135) but no vaccine exists to combat serogroup B (menB); nor is there a vaccine available against N. gonorrhoeae. One target for vaccine development against menB and N. gonorrhoeae is the iron transporters found on the pathogens’ surfaces.  Cut off their access to iron and these pathogens cannot survive.

Determining how RNA (ribonucleic acid) folds, or "ravels", may offer a key to un-raveling how and why anomalies occur in the human genome. RNA is now known to play a pivotal role in gene silencing, gene shuffling, protein regulation and disease. However in contrast to proteins, very little is known about how RNA takes its three-dimensional shape and under certain circumstances works as an enzyme. Getting a good look at RNA in the process of folding from its initial 1-D "ribbon" state, into a 3-D "knot" (the form in which RNA is biologically functional) would be very valuable information

DNA is softer and stretchier than previously believed, at least on the short length scales of up to 20 base pairs. This finding is the result of a recent study conducted in part at SSRL's biological small-angle x-ray scattering Beam Line 4-2 by a team of researchers from Stanford University. The results were published in the October 17 edition of the journal Science.

While the normal function of human prion protein (PrP) remains a mystery, the results of abnormal PrP are quite well known. Misfolded PrP (denoted PrP^Sc) leads to diseases such as Creutzfeldt-Jakob disease, mad cow disease, and scrapie in sheep. In these diseases, the protein acts like an infectious agent, recruiting other PrP to become PrP^Sc without requiring any involvement from nucleic acids or any other molecules. Many PrP^Sc molecules can bind together to form amyloid structures, similar to those that contribute to a wide variety of diseases including Alzheimer's and Parkinson's.