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Enzymes chemically transform small molecules. Understanding these transformations can help us figure out why some small molecule drugs are active in some patients, but inactive in others. Additionally, these reactions explain why people digest dietary molecules from food differently. Finally, knowledge of how enzymes change molecules can help us to optimize drug leads for the highest activity and least toxicity. Mass spectrometry is a high throughput technique for collection of reaction data between 100s of enzymes and 10000s of substrates. However, single stage mass spectrometry (MS1) only provides the monoisotopic mass of the molecules, and even tandem mass spectrometry (MS2) is usually not enough for full-characterization of novel small molecules. Multistage mass spectrometry (MS3, MS4 and beyond) is a power technique for extracting information about the structure of known and novel small molecules. The goal of this project is to (i) design protocols for acquisition of MS3 and MS4 on a large number of known and novel small molecules (e.g. reaction of P450 enzymes with libraries of substrates, with focus on lipids, sterols, dietary molecules and other xenobiotics), and (ii) mass-guided HPLC-based purification of novel products. The postdoctoral researcher will be closely collaborating with other computational mass spectrometry researchers in Mohimanilab for data analysis. This is a collaboration with Dr. Vallim Laboratory at UCLA.
Job Responsibility:
Design protocols for acquisition of MS3 and MS4 on a large number of known and novel small molecules (e.g. reaction of P450 enzymes with libraries of substrates, with focus on lipids, sterols, dietary molecules and other xenobiotics)
Mass-guided HPLC-based purification of novel products
Closely collaborating with other computational mass spectrometry researchers in Mohimanilab for data analysis
Requirements:
Ph.D. or equivalent degree in Chemistry, Biochemistry or Chemical Biology
Ability to work independently and strong interpersonal skills
Experience with tandem and multistage mass spectrometry is required (e.g. Fusion, Lumos, Eclipse or Ascend instruments)
Experience with mass-guided HPLC-based purification is required (e.g. Infiniti 1260 or 1290 with mass detector)
Nice to have:
Experience with enzyme assays would be a plus
Experience with high throughput screening would be a plus