First the players. The insect in question is the citrus pest mealybug, Planococcus citri. Like aphids and other insects that feed on the amino-acid poor phloem sap of plants, mealybugs require endosymbiotic bacteria to provide them these essential nutrients. They carry these working partners in the cytoplasm of specialized cells, the bacteriocytes. As for the bacteria, the ‘host’ is β-proteobacterium Candidatus Tremblaya princeps, called Candidatus because it cannot be grown in the lab. Its name won’t be italicized until this rule changes. It better, because T. princeps (I use italics in defiance) will never be able to grow independently as it has the smallest of all known cellular genomes: 139 kb. Living inside of it is the newly named γ-proteobacterium, Moranella endobia (also a ‘candidatus,’ but we’ll dispense with that.) The genus name honors the famed endosymbioticist Nancy Moran. The host Tremblaya cells are quite large, 10-20 μm wide; nested within are the Moranella, each 3-6 μm long and with a Gram-negative-like double membrane structure. Moranella has the audacity to possess a genome about four times larger than that of its host, a case, ostensibly, of genomic chutzpah. (» more)
1. Because it is interesting.
2. Because of the sassy science writing.
…He and Pascal George—a younger colleague whom Kaplan described as “sympathetic and brilliant”—started by building wooden models, including ones for Valium, Halcion, and zopiclone. Colored one-inch spheres, representing atoms, were connected by thin rods, creating models the size of a shoebox. This was a more empirical, architectural approach than is typical in a lot of pharmaceutical chemistry. Kaplan and George tried to identify what these molecules had in common, structurally, that allowed them to affect the brain in the same way. Kaplan told me that their thinking wasn’t wildly creative, but it was agile: “You know, at that time it was maybe clever, because you have no computer. Now it’s routine work.”
George wrote a report describing a few possible types of new chemical compounds. Working separately, they built molecules of the first two types: about ten of one, five of the other. These were unpromising. A third series, made by George, looked better. When it was tested on animals, Kaplan said, “it was clear that it would be a great success. After the very first compound, I knew.” But in 1980, while this work was still under way, Kaplan was taken off the project. In his account, Synthélabo, eager to get rid of him, “didn’t want to give me the merit of the invention.” From then on, George ran the research. Kaplan heard only rumors about how the compounds were testing.
That fall, Synthélabo applied for a French patent on a series of seventy-seven compounds. The company knew that one of the compounds had far more pharmaceutical promise than the others, but did not need to disclose this to industry competitors. So the star molecule was also hidden from Kaplan, even though his name was at the top of the document. He showed me the patent. “I was named the first inventor, but did not have the results of the compound I proposed!” he said. He looked down a list of seventy-seven chemical formulas, and pointed to the seventy-fifth: this was Ambien. (» more)
This is an excerpt from a fascinating look at suvorexant— a Merck drug that seeks to fight insomnia without the side-effects of Ambien— from early research to drug development to FDA trials.
my dream protein class
- study the structure and function of existing proteins
- design a new protein, residue by residue
- visualize the 3D structure of your protein
- your protein should perform a specific task in a specific environment
- name your protein!