The rise of multiply drug resistant bacteria creates an urgent need for new antibiotics and novel antibiotic targets. IMPDH, a key enzyme in the biosynthesis of RNA/DNA precursors, is a target for cancer therapy that has not been exploited in antibiotic development. In their recent paper in Chemistry & Biology entitled Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases, Prof. Lizbeth Hedstrom and Brandeis postdocs Deviprasad Golapalli, Iain MacPherson and Suresh Gorla show that selective inhibitors of IMPDH from the protozoan parasite Cryptosporidium parvum also exhibit antibacterial activity. This work could lead to novel treatments for a wide variety of bacterial infections, including some of the most devastating and troubling human pathogens: Mycobacterium tuberculosis, drug-resistant Staphylococcus aureus (e.g. MRSA and VRSA), drug resistant Streptococcus pneumoniae and select agents such as Bacillus anthracis, Burkholderia mallei/pseudomallei and Francisella tularensis. Importantly, these compounds will spare some commensal bacteria, which should decrease side effects and slow the rise of resistance. This work suggests that IMPDH-targeted inhibitors can be developed into a new class of broader spectrum antibiotics.
Novel IMPDH inhibitors are candidates for antibacterial drugs
2010 Beckman Scholars
Brandeis was recently awarded a grant from the Arnold and Mabel Beckman Foundation through their Beckman Scholars Program. This grant will support two students each through two summers and one academic year of undergraduate research.
Philip Braunstein and Jessica Hutcheson have been named the 2010 Beckman Scholars. Braunstein (class of 2012) is a Biochemistry major identifying parasite-selective inhibitors of pyrimidine biosynthesis in the Hedstrom laboratory. Hutcheson (2011) is a Biochemistry/Neruoscience major investigating the molecular processes that determine memory in the Griffith laboratory.
Congratulations to the winners!
“All you need is a cow and a centrifuge…”
“…to harvest enough oocysts to infect a small city”.
Read more about the Hedstrom lab‘s research on Cryptosporidium in this press release from FASEB.
Biochemistry Senior Research Talks
It’s also the season for Senior Honors / Masters Thesis talks…
DEPARTMENT OF BIOCHEMISTRY
Annual Senior Research Talks
2009/2010 Biochemistry Honors and BS/MS Candidates
Friday, April 23, 11:30-1:30pm – G-zang 122
Clarence Friedman – BS/MS
Characterization of 1-d-deoxyxylulose reductoisomerase
Advisor: Dan Oprian
Stefan Isaac – BS/MS
Functional Characterization and in silico Modeling of HlyU
Advisors: Dagmar Ringe/Greg Petsko
Seth Lieblich BS/MS
Bacterial Gene Repressors
Advisor: Dagmar Ringe
Miranda Patton BS/MS
Mutation of the Active Site of IMP Dehydrogenase, to Find a Novel Mutant and Create a Hybrid GMP Reductase
Advisor: Liz Hedstrom
Nat Lazar BS
We are superfamily: bioinformatic and biochemical analyses of protein evolution
Advisor: Douglas Theobald
Kanchana Ravichandran BS
Formation of heterotetramers between the human isozymes of Inosine 5’-Monophosphate Dehydrogenase
Advisor: Liz Hedstrom
Seth Robey BS
Streamlining C1C-0 Purification and Examining the pH Dependence of an Amino Acid Transporter
Advisor: Chris Miller
Kenta Yamamoto BS
The Type-1 Insulin-Like Growth Factor in Cancer and Hematopoiesis
Advisor: Ruibao Ren
Everyone is welcome and encouraged to come. Pizza will be provided.
PhD Defense Season
It’s the season for PhD defenses…
- Apr 20: Megan Zahniser (Biochemistry), On the structure of Benzaldehyde Dehydrogenase, a Class 3 Aldehyde Dehydrogenase from Pseudomonas putida – 2pm, Rosenstiel Penthouse
- Apr 21: Chris Hoefler (Biochemistry/Bioorganic Chemistry). Inhibitors of IMPDH: Tools for Probing Mechanism and Function – 3:40 pm, Gerstenzang 122
- Apr 22: Tepring Piquado (Neuroscience), Language and the aging brain – Thu 4/22/2010, 2 pm, Volen 201
- Apr 23: Suvi Jain (Molecular and Cell Biology), Regulation of DNA Double-Strand Break Repair by the Recombination Execution Checkpoint in Saccharomyces cerevisiae – 3:30 pm, Rosenstiel 118
- Apr 29: Ben Cuiffo (Molecular and Cell Biology), Targeting RAS palmitoylation in hematological malignancies – 2 pm, Abelson 131
Prodrug activation by Cryptosporidium thymidine kinase
Xin Sun, a Biochemistry grad student from the Hedstrom Lab, discusses her recent paper in J. Biol. Chem.:
I get to say the word “diarrhea” within the first 1-2 sentences of
talking to a stranger about what I work on, and the look I get back is always amusing. We work on developing inhibitors against a human pathogen called Cryptosporidium parvum, a nasty little parasite that causes the aforementioned diarrhea. We specifically zoomed in on the parasite’s nucleotide synthesis pathways to look for potential drug targets. Our recent paper looked at the enyzme thymidine kinase from the parasite, and studied its role in activating a prodrug that we showed to be effective in reducing parasite load in both a cell culture assay, and in a mouse model.
