Development of small-molecule modulators of the transcription factor brachyury

Written in collaboration with Tigran M. Abramyan (Alexander Tropha’s lab at UNC Chapel Hill) In my previous open lab notebook entry I described the in silico approach using the program SparkTM to grow fragments found to co-crystallize within binding site A of the transcription factor brachyury to compounds with hopefully higher binding potency. The overall aim Read More …

A Gentle Introduction to The Ligandable Genome Project

Previously in our lab, Jiayan Wang et al. worked on a project related to the druggable genome. In her project, she evaluated the druggability of protein domains found in the human genome using protein structures bound to druglike ligands. The left panel in Figure 1 demonstrates her workflow to define ligand binding pockets. To build Read More …

PILOT RESULTS: Grin1 Y647S Project

Grin1 p.Tyr647Ser Project Background. Grin genes across species encode for proteins that make up the different NMDA receptor subunits. GRIN1 mutations (usually heterozygous) are associated with intellectual disability with epilepsy in humans, including the rare p.Tyr647Ser (Y647S) variant. This missense mutation occurs in the M3 helix of the transmembrane domain of GRIN1 which, importantly, is conserved between human GRIN1 and mouse Read More …

Safety first when working in the lab

Do you know what the image above represents? I will give you a clue, it relates to lab safety. Any takers? Still nothing? Well, this my friends represents corrosive materials. This group includes many strong acids and bases and was a question I got wrong in my safety exam today (gasp, shock, you failed Tom). Read More …

Purification of HTT N-HEAT_81-1643 construct with different buffer conditions

In my previous purification of the HTT N-HEAT_81-1643 construct, I showed that an additional heparin step did not remove any traces of nucleic acid material, changed purity or oligomeric state of the sample. Additionally, my DLS results showed that this construct forms large particles in solution. Thus, the DLS results in combination with the gel filtration Read More …

Rise of the machines….and Lab automation

Last week this was my view. This week nothing but wintry snow and cold everywhere. Oh, how I miss the sunnier climes of San Diego. I think I will add one more resolution to my first blog, spend some time every winter somewhere sunny, as this cold really gets into the bones. Anyways, I wasn’t Read More …