Protein science “best paper” awards to Mark Landau and Brian Ziemba

Abstract

Warmest congratulations to Brian Ziemba (right) and Mark Landau (left), the recipients of the Protein Society's “Best Paper” awards. At the beginning of each year, two “best papers” are selected from articles published in Protein Science during the preceding 12 months. A junior author (typically the first author) is designated as the award winner and invited to give a talk at the following Annual Protein Society Symposium. Mark Landau received his Bachelor of Science degree in Chemical Biology from UC-Berkeley and Ph.D. in Yale's Department of Molecular Biophysics and Biochemistry. As a graduate student, and now as a postdoctoral associate, his research in the laboratory of Professor Karen Anderson has focused on the mechanisms of enzymes relevant to disease therapy, including HIV-1 reverse transcriptase, the human cytidine deaminase APOBEC3G, and the bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the parasite Toxoplasma gondii. In the future, he hopes to pursue a career in academic research and study the function of enzymes with clinical relevance. Mark's award-winning article1 was the result of probing the TS-DHFR structure and function to aid the design of allosteric inhibitors with increased selectivity. This led to the discovery of peptide inhibitors, which mimic β-strands at the enzyme's dimer interface, that bind specifically to the apo-enzyme form of the parasitic TS-DHFR and inhibit both TS and DHFR activity but do not affect human TS or DHFR. Fluorescence spectroscopy revealed that these peptides take advantage of the enzyme's unique molecular motions to bind and trap it in an inactive conformation. Dr. Anderson commented that “The aspect of Mark's project described in the article was taken up completely as his own initiative. I was supportive but skeptical that it would work. Thankfully, as is often the case, as PIs, we are wrong and the design worked beautifully.” Brian Ziemba's undergraduate studies (University of Colorado, Boulder) focused on molecular biology and biochemistry with the intention of going into medicine. Along the way, he became involved in several undergraduate independent research projects and his interests became more aligned with scientific research. After studying clinical laboratory science (OHSU, Portland, OR), and working nights for 3 years as a medical technologist in Reno, NV, and then in Lafayette, CO, he realized that he belonged in a more research-oriented environment. As a graduate student at the University of Colorado Denver (Anschutz Medical Campus), he joined the lab of Professor David N.M. Jones, where he became interested in structural biology. His main thesis project involved using NMR, X-ray crystallography, and fluorescence methods to explore ethanol:protein interactions in ethanol-sensitive proteins, such as protein kinase Cδ and the GABAρ receptor. Although half of the lab focused on alcohol sensitivity, the other half worked toward the goal of understanding the molecular events of olfactory signaling that guides feeding behavior of the mosquito Anopheles gambiae, the primary vector of the most dangerous form of malaria. This required studies on multiple odorant binding proteins (OBPs), which function to complex with human odorants in order to inform host-seeking behavior, and thus malaria transmission. Because of his prior experience, Brian could help in cloning OBP20 and then went on to pursue crystallographic studies. Interestingly, OBP20 crystals formed differently in response to varying crystallization conditions, yielding insights into the mechanism of odorant ligand binding and release, which occurs in mosquito olfaction and host-seeking processes.2 Resolution of the two states of OBP20 that exist in the process of mosquito olfaction may ultimately be important for knowing which state to target in order to inhibit activity. Prof. Jones comments that “Brian is the perfect example of a great lab member. He takes on jobs completely unknown to me, to help out another lab member. He has continued to provide input and ideas even after leaving the lab.” Brian is currently a postdoc in the lab of Joseph Falke. He says that his future plans are undetermined at this point. As he puts it “Industry appeals to me as a profession where I could potentially contribute to amelioration or detection of human disease while academia continues to draw me to a setting where scientific curiosities and interests are more easily pursued.”