Cancer cells often overexpress glutaminase enzymes, in particular glutaminase C (GAC), which resides in the mitochondria and catalyzes the hydrolysis of glutamine to glutamate.  High levels of GAC have been observed in aggressive cancers and the inhibition of its enzymatic activity has been shown to reduce their growth and survival, both in vitro and in mouse models.  Numerous GAC inhibitors have been reported, with the most heavily investigated being a class of compounds derived from the small molecule BPTES (bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide).

WebsEdge is an international company specializing in providing educational TV channels at technical conferences. A production crew visited CHESS on January 14, conducting interviews and recording activities here. Through highly skilled editing, the resulting several hours of “footage” was distilled down into a 5-minute video presenting the essence of MacCHESS to the public. We retain the raw recordings for use in future presentations.

Gillilan, together with a former MacCHESS postdoc, Soren Skou and long time CHESS user, Nozomi Ando have distilled much of their knowledge into a Nature Protocols article.

To understand this critical cellular process, biologists are studying the fine details of the structural changes involved, and how they are regulated. RNAP complexes vary from one species to another, but a core subset of proteins is found throughout archaeal and eukaryotic life forms. Comparison of archaeal and eukaryotic proteins reveals how structural motifs have been modified during evolution, so that function is maintained while regulation has become more complex in eukaryotic species.

What did the scientists discover?

He has used X-ray crystallography at CHESS, as well as other resources, to decipher the operation of the Golgi apparatus, the cell's sorting depot. Read the announcement from the Guggenheim Foundation here and a story from the Cornell Chronicle here.

And, the tiny beam has to hit the tiny crystal. The location of the beam can be well determined and doesn't change, but how do we know where the crystal is?

There are four known families of membrane-immersed proteases (enzymes which break protein chains); all four carry out important functions and damage to them is implicated in pathologies including cancer, Parkinson's disease, impaired resistance to parasites, and more. When a mutation results in overactivity of a membrane protease, an inhibitor of the protease can be effective treatment for a disease. Designing such inhibitors has proven difficult, largely because of incomplete understanding of the catalytic process in the intramembrane environment.

Usually, HPC has negligible effect on the crystal structure. Occasionally, it causes a small change in packing of the molecules in the crystal. For crystals containing a lot of solvent, pressure may cause them to collapse, destroying their diffraction. HPC on crystals of Snf7, however, results in a large change in molecular packing without destroying the crystallinity. In fact, the pressure-cooled crystals diffract better than the normally cooled crystals, in spite of a 30% decrease in unit cell volume!

The MLL3 (mixed lineage leukemia 3) protein, for example, is a member of the SET1 family of histone-modifying enzymes, which plays a critical role in regulating transcription of genetic information in humans. Misregulation of histone modification is associated with different cancers and developmental disorders. MLL1 is well studied and has been used to predict how MLL3 and other SET1 proteins function, but the validity of these predictions is uncertain – do all family members really work the same way?