The Brown lab developed a unique small molecule screen
based on conditional lethality of specific steps in the wall teichoic
acid pathway to identify a new inhibitor of an important enzyme
needed to synthesize a common component key to several cell
wall pathways. Farha MA, Czarny TL, Myers CL, Worrall LJ, French
S, Conrady DG, Wang Y, Oldfield E, Strynadka NC, Brown ED.
Antagonism screen for inhibitors of bacterial cell wall biogenesis
uncovers an inhibitor of undecaprenyl diphosphate synthase.
Proc Natl Acad Sci U S A. 2015 112( 35):11048-53.
The Burrows lab characterized a novel bacterial sensory
system used to monitor the level of type IV pilin subunits in the inner
membrane, suppressing further synthesis under conditions of high
inventory. Kilmury SL, Burrows LL. Type IV pilins regulate their own
expression via direct intramembrane interactions with the sensor
kinase PilS. Proc Natl Acad Sci U S A. 2016 113( 21):6017-22.
The Guarné lab used clever biochemical tricks to trap a weak
interaction between two components required for DNA mismatch
repair in bacteria, allowing them to perform structural studies and
to measure the change in activity resulting from the interaction.
Pillon MC, Babu VM, Randall JR, Cai J, Simmons LA, Sutton MD,
Guarné A. The sliding clamp tethers the endonuclease domain of
MutL to DNA. Nucleic Acids Res. 2015 43( 22):10746-59.
The Li lab showed that in vitro selection could rapidly
evolve a non-enzymatic sequence into one encoding an
enzymatic activity. Deep sequencing allowed them to trace the
trajectory of the enzyme’s evolution, providing insight into how
the wide diversity of activities in nature may have arisen.
Gysbers R, Tram K, Gu J, Li Y. Evolution of an Enzyme from a
Noncatalytic Nucleic Acid Sequence. Sci Rep. 2015 5:11405.
The Magarvey lab developed a powerful new bioinformatic
tool called PRISM that can accurately predict the chemical
properties and structures of natural products directly from
genomic information. This popular tool will accelerate the
discovery of new antibiotics. Skinnider MA, Dejong CA, Rees
PN, Johnston CW, Li H, Webster AL, Wyatt MA, Magarvey NA.
Genomes to natural products PRediction Informatics for Secondary
Metabolomes (PRISM). Nucleic Acids Res. 2015 43( 20):9645-62.
The Singh lab, with collaborators from the Bhatia, Doble, and
Hassell labs, identified a small molecule inhibitor of glioblastoma
proliferation and showed that it preferentially targets CD133(+)
cells, blocking their self-renewal. Venugopal C, Hallett R, Vora P,
Manoranjan B, Mahendram S, Qazi MA, McFarlane N, Subapanditha
M, Nolte SM, Singh M, Bakhshinyan D, Garg N, Vijayakumar T, Lach
B, Provias JP, Reddy K, Murty NK, Doble BW, Bhatia M, Hassell JA,
Singh SK. Pyrvinium Targets CD133 in Human Glioblastoma Brain
Tumor-Initiating Cells. Clin Cancer Res. 2015 21( 23):5324-3
The Sloboda lab showed that treating pregnant rats with
antidepressants (SSRIs) had negative impacts on the fertility of
the resulting female offspring, adding growing evidence to the
concept that interventions during pregnancy have long lasting
implications for subsequent generations. Moore CJ, DeLong
NE, Chan KA, Holloway AC, Petrik JJ, Sloboda DM. Perinatal
Administration of a Selective Serotonin Reuptake Inhibitor Induces
Impairments in Reproductive Function and Follicular Dynamics in
Female Rat Offspring. Reprod Sci. 2015 22( 10):1297-311.
The Surette group recently showed that with careful
anaerobic technique, fresh samples, and a range of defined
media, the majority of bacteria found in the human gut
microbiome can be cultured – more than were found to be
present even by deep sequencing methods. Among the species
they recovered were several on the Human Microbiome
Project’s ‘Most Wanted’ list. Lau JT, Whelan FJ, Herath I,
Lee CH, Collins SM, Bercik P, Surette MG. Capturing the
diversity of the human gut microbiota through culture-enriched
molecular profiling. Genome Med. 2016 Jul 1; 8( 1):72.
The Wright lab published the results of a comprehensive
screen of 3600 small molecules combined with sub-inhibitory
concentrations of six different antifungal molecules, against a set
of important fungal pathogens. The resulting dataset provides
important leads for treatments that can target drug resistant
fungal pathogens. Robbins N, Spitzer M, Yu T, Cerone RP,
Averette AK, Bahn YS, Heitman J, Sheppard DC, Tyers M, Wright
GD. An Antifungal Combination Matrix Identifies a Rich Pool of
Adjuvant Molecules that Enhance Drug Activity against Diverse
Fungal Pathogens. Cell Rep. 2015 Nov 17; 13( 7):1481-92.
In November, Deb Sloboda was honoured with the
2015 Nick Hale Award from the International Society for
Developmental Origins of Health and Disease (DOHaD)
for her outstanding contributions to DOHaD research. The
award is given every two years to “a young and emerging
investigator who is a DOHaD member and has made an
outstanding scientific contribution to the DOHaD field.”
Lori Burrows and Jon Schertzer were also recognized
based on enthusiastic current and former trainee
nominations with FHS Excellence in Graduate
Supervision awards, awarded at the 2016 FHS Research
Plenary in May.
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