Biochemistry and Molecular Biophysics

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Logo for the Dept of Biochemistry and Molecular Biophysics at Washington University in St. Louis, MO
The 2014-BMB/MBCP Retreat

Carl Frieden Portrait Unveiling

2015 DeGutis Award

Student Liaison Committee

Welcome to Summer Hawaiian Shirt Contest

Welcome to New BMB Arrivals

Research Awards

Latest Publications
Carl Frieden Portrait Unveiling

On June 5, 2015 the department held a Reception to unveil a portrait of Professor Carl Frieden.  The reception was held to recognize Dr. Frieden’s accomplishments and service to our department, Washington University and the scientific community.  Many family and friends flew in for this special event.  After the reception, the department held a dinner at Scape American Bistro for Dr. Frieden’s family, close friends and faculty in the Department of Biochemistry and Molecular Biophysics, and their spouses. For more photos.

Carl Frieden was born and raised in New Rochelle, New York. He obtained his B.A. degree from Carleton College and his Ph.D. in Chemistry from the University of Wisconsin under the mentorship of Robert A. Alberty. In 1955, Dr. Frieden joined the Department of Biological Chemistry at Washington University School of Medicine as a postdoctoral fellow to work with Dr. Sidney Velick. He was hired by Carl Cori as an Instructor in 1957 and promoted to full professor in 1967. Dr. Frieden has served both as Interim Head (from 1987 to 1990 and from 1997 to 2000) and Head (from 2000 to 2005) of the Department. Among other awards, he has received the Carl and Gerty Cori Faculty Achievement Award and the Second Century Award from Washington University. He has also been awarded the Peter Raven Lifetime Achievement Award from the St. Louis Science Center as well as the Christian B. Anfinsen Award from the Protein Society. He was elected to the National Academy of Sciences in 1988 and to the American Academy of Arts and Sciences in 2004. From 1995-2000 he was an Alumni Endowed Professor and, from 2000 to 2005, the Wittcoff Endowed Chair of the Department of Biochemistry and Molecular Biophysics. He served as Director of the Medical Science Training Program (MSTP) from 1986-1991.    
 Dr. Frieden has not only contributed to the scientific community but also to our community as a whole through music and art programs.  In 1975, Dr. Frieden initiated and ran a program called Music in Moore that invited (mostly) members of the St. Louis Symphony to play over the lunch hour in Moore Auditorium. There were 3-4 concerts each year, over the span of 10 years. In 2000, Dr. Frieden initiated and ran a program to exhibit art work around the medical school campus with both inside and outside displays. There were 5 such exhibits over the span of five years.

His current research deals with two problems: the investigation and understanding of the properties of apolipoproteins E (apoEs), the major risk factor for the development of late onset Alzheimer’s disease and a bacterial system that leads to formation of biofilms.
2015 DeGutis Award

Congratulations to Robin Shields-Cutler!

On June 9, 2015, Robin Shields-Cutler was awarded the 2015 Ceil M. DeGutis Prize in Chemical Biology/Medicinal Chemistry.  Robin presented his research at the DeGutis Presentation on June 9th entitled: How the human urinary metabolome supercharges antimicrobial defenses.  Robin graduated this Spring from the Molecular Microbiology and Microbial Pathogenesis graduate program.  He has accepted a 1-year position as Assistant Professor of Biology at Grinnell College, in Grinnell, IA, that begins this fall. After that, he'll complete his postdoctoral research.

Robin was nominated by his Thesis Mentor, Dr. Jeff Henderson, for his work on protein-metabolite interactions which established the basis for a new pharmacologic approach to urinary tract infections that may be combined with other antivirulence approaches in this area. 

Robin’s work has focused on a soluble innate immune protein called siderocalin (also known as lipocalin-2/Lcn2, neutrophil gelatinase-associated protein/NGAL, or 24p3) that is released from white blood cell granules or synthesized de novo in epithelial cells following pro-inflammatory stimuli. For the past decade, siderocalin (SCN) has been known to inhibit E.coli growth by binding ferric ion complexes of the siderophore enterobactin, a bacterial iron acquisition molecule. Robin identified discrepancies in the literature suggesting a different mode of action in human urine, an environment relevant to urinary tract infections (UTIs). He pursued this line of study and found that in urine, SCN instead inhibits E.coli growth by binding ferric ion complexes of distinctive urinary metabolites. He developed a biophysical screen capable of identifying these SCN-binding metabolites in human urine and has used mass spectrometry-based metabolomics approaches to determine their structures.

In this distinctive urinary context, Robin found that the E.coli siderophore enterobactin becomes critical for resisting SCN –the opposite of its previously understood role. He then showed that a previously known lead compound under development as an M. tuberculosis antivirulence agent potentiates SCN’s antibacterial activity by inhibiting enterobactin biosynthesis. This repurposed compound now serves as a distinctive lead for a new pharmacologic strategy to potentiate an innate antibacterial response.

About the award: The Ceil M. DeGutis Prize was endowed by Kathryn and George Gokel in memory of Kathryn's grandmother. The DeGutis Prize is awarded to a senior graduate student, in their fifth or sixth year of graduate study, who has made a significant contribution to the field of Chemical Biology or Medicinal Chemistry disciplines broadly defined.  A $250 cash prize and plaque is presented in the awardee. 
Student Liaison Committee
Pictured: top left: Alex Holehouse, Josh Rackers and Sukrit Singh
bottom left: Anne Robinson, Nicole Fazio and Melanie Sparks

The BMB and CMBP graduate students recently held elections for the Student Liaison Committee. The new officers are: Chair: Anne Robinson and Co-Chair: Sukrit Singh; Science Fridays Committee: Nicole Fazio and Sukrit Singh; Biophysical Evenings Committee: Melanie Sparks and Anne Robinson; Student Invited Seminar Speaker: Alex Holehouse and Student Outreach: Josh Rackers. 

Welcome to Summer Hawaiian Shirt Contest
On May 29th we had our "Welcome to Summer Happy Hour'. Featured food: hamburgers, hot dogs, veggie burgers and more. The winners of the Hawaiian Shirt Contest were Josh Brettmann and Tom Ellenberger. They each received their own box of Flavor-Ice. 
BMB Department Welcomes...
Ryan Chugani-Research Technician in Jim Janetka's lab.
Nicole Fazio-Graduate Student in Tim Lohman's lab.
Michel Grigoriev-Assistant Professor in Tom Ellenberger's lab.
Laurel McGrane-Visiting Scientist in Jim Janetka's lab.
Grace Ramena-Postdoctoral Research Associate in Linda Pike's lab.
Summer Staff:
Kim Gerik (Burgers lab)
Neelanjan Lakshman (Barnes lab)
Katelyn Moeder (Bowman lab)
Research Awards

Joshua Solokoski, PhDhas been awarded a 2 year postdoctoral fellowship from the American Cancer Society for his research entitled “Helicase-driven reorganization of single strand DNA binding proteins on DNA”.

Upcoming Events:

July 10, 2015
BMB Science Fridays
Rotation Talks: Elizabeth DeLassus & Elisa Murray

July 17, 2015
BMB Science Fridays
Katie Hart (Bowman lab)-TBA

July 24, 2015
BMB Science Fridays
Happy Hour

July 31, 2015
BMB Science Fridays
John Robinson (Beverly lab)-TBA

August 7, 2015
BMB Science Fridays
Happy Hour

August 14, 2015
BMB Science Fridays
Josh Sokoloski (Lohman lab)-TBA

August 21, 2015
BMB Science Fridays
Happy Fall Happy Hour

Latest Publications:

Bowman, G.R. Accurately modeling nanosecond protein dynamics requires at least microseconds of simulation. J Comput Chem (E-pub ahead of print.) (2015).

Wanrooij, P.H, and Burgers, P.M. Yet another job for Dna2: Checkpoint activation. DNA Repair (E-pub ahead of print.) (2015).

Koc, K.N., Stodola, J.L., Burgers, P.M. and Galletto, R. Regulation of DNA polymerase delta-mediated strand displacement synthesis by 5-flaps. Nucleic Acid Research 43:4179-4190 (2015).

Sparks, J.L. and Burgers, P.M. Error-free and mutagenic processing of topoisomerase 1-provoked damage at genomic ribonucleotides. EMBO J. 34:1259-1269 (2015).

Williams, J.S., Clausen, A.R., Lujan, S.A., Marjavaara, L., Clark, A.B., Burgers, P.M., Chabes, A. and Kunkel, T.A. Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading-strand specific. Nat Struct Mol Biol. 22:291-297 (2015).

Pascal, J.M. and Ellenberger, T. The rise and fall of poly(ADP-ribose): An enzymatic perspective. DNA Repair (E-pub ahead of print.) (2015).

Chen, X., Kim, IK., Honaker, Y., Paudval, S.C., Koh, W.K., Sparks, M., Lis, S., Piwnica-Worms, H., Ellenberger, T. and You, Z. 14-3-3 proteins restrain the Exo1 nuclease to prevent over-resection. J Biol Chem 290:12300-12312 (2015).

Ghisays, F., Brace, C.S., Yackly, S.M., Kwon, H.J., Mills, K.F., Kashentseva, E., Dmitriev, I.P., Curiel, D.T., Imai, S.I. and Ellenberger, T. The N-terminal domain of SIRT1 is a positive regulator of endogenous SIRT1-dependent deacetylation and transcriptional outputs. Cell Rep. S2211-1247:00182-00185 (2015).

Rowe, R.A., Pryse, K.M., Asnes, C.F., Elson, E.L. and Genin, G.M. Collective matrix remodeling by isolated cells: Unionizing home improvement do-it-yourselfers. Biophys J 108:2611-2612 (2015).

Fishburn, J., Tomko, E. Galburt, E.A. and Hahn, S. Double-stranded DNA translocase activity of transcription factor TFIIH and the  mechanism of RNA polymerase II open complex formation. PNAS (E-pub ahead of print.) (2015).

Feldmann, E.A., De Bona, P. and Galletto, R. The wrapping loop and RCT domain of yeast Rap1 modulate access to different DNA binding modes. Journal of Biological Chemistry 290:11455-11466 (2015).

Hall, K.B. Mighty tiny. RNA 21:630-631 (2015).

Rau, M.J. and Hall, K.B. 2-Aminopurine fluorescence as a probe of local RNA structure and dynamics and global folding. Methods Enzymol. 558:99-124. (2015).

Sasaki, Y., Margolin, Z., Borgo, B., Havranek, J.J. and Milbrandt, J. Characterization of Leber's congenital amaurosis-associated NMNAT1 mutants. J Biol Chem (E-pub ahead of print.) (2015).

Franco, F.M., Jones, D.E., Harris, P.K.W., Han, Z., Wildman, S.A., Jarvis, C. and Janetka, J.W. Structure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets. Biooranic & Medicinal Chemistry SO968-0896:00268-0 (2015).

Kuster, D.J., Liu, C., Ponder, J.W., Marshall, G.R. High-resolution crystal structures of protein helices reconciled with three-centered hydrogen bonds and multipole electrostatics. PLoS One 10:e0123146 (2015).


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