Yousif Shamoo ('13)

Rice University

6100 Main Street

Houston, TX  77005  

Phone: 713-348-5493

Fax: 713-348-5154    

E-mail: shamoo@rice.edu

Speaker’s URL:  http://www.bioc.rice.edu/~shamoo/shamoolab.html

LECTURE TOPICS AND DESCRIPTIONS

Evolutionary Fates Within a Microbial Population: The Essential Role for Protein Folding During Natural Selection

In Nature, evolution occurs through the continuous adaptation of a population to its environment.  The success or failure of organisms during adaptation is based upon changes in molecular structure that give rise to changes in fitness that dictate evolutionary fates within a population.  While the conceptual link between genotype, phenotype and fitness is clear, the ability to relate these complex adaptive landscapes in a quantitative manner remains difficult.  We have constructed a model system in Geobacillus for the study of adaptation to temperature through a single gene that serves as a “weak link.”  Using this system, one can study the adaptation at the level of protein function and how it correlates to changes in adaptation (published in Molecular Systems Biology (MSB) 2010 Jul 13; 6:387 and was the most downloaded MSB paper in

August 2010).                                            

Experimental Evolution as a Tool for Completing the Link Between Genomics, Biochemistry and Prediction in Antibiotic Resistance  

Experimental evolution can provide a powerful experimental framework for probing how adaptation can be quantitated and modeled for prediction of complex and important phenomena such as drug resistance.  Vancomycin Resistant Enterococci (VRE) are important multi-drug resistant hospital-associated pathogens that often affect critically ill patients.  Daptomycin (DAP) (Cubicin™, Cubist Pharmaceuticals) is a novel lipopeptide which is approved for use against Methicillin Resistant Staphylococcus aureus (MRSA) and VRE.  Our collaborator, Dr. C. Arias, (University of Texas Health Science Center) has identified four genes associated with reduced daptomycin susceptibility using comparative whole genome analysis of DAP-susceptible and resistant clinical strains.  We have used in vitro experimental evolution to reproduce these clinical findings and map out the adaptive network of daptomycin resistance in the clinical strain.  We are elucidating the physicochemical mechanisms of DAP-resistance and building genomic changes can then be mapped as a network of changes linked to their biochemical origins.  

Correlating Changes in Structure and Function of Bacteroides thetaiotaomicron TetX2 to Fitness During Adaptation to Minocycline

The combination of experimental evolution to identify adaptive changes in proteins undergoing selection and their subsequent physicochemical characterization provides a physical basis for linking protein structure and function to organismal fitness.  This is particularly relevant for the study of antibiotic resistance where the evolution of drug resistant bacteria is clinically important.  We have determined the structure of the B. thetaiotaomicron TetX2 at 2.8 Å resolution and its kinetic properties.  Experimental evolution was then used to identify an adaptive mutation (tetX2T280A) within a bacterial population that confers higher resistance to minocycline and tigecycline.  Strains carrying tetX2T280A have higher growth rates at intermediate but not lower concentrations of minocycline that correspond to the conditions when the mutant was first observed.  The temperature dependent kinetic properties of an adaptive mutant in tet(X2) conferring greater resistance to MCN is directly correlated to changes in growth rate and subsequent evolutionary success.  Together, experimental evolution and biochemistry can provide the foundation for quantitative insights in the evolution of protein structure and function.

BIOGRAPHICAL SKETCH

Dr. Shamoo is an Associate Professor whose formal training is in structural biology and biophysics but whose most recent work is at the interface of evolutionary biology and biophysics.  By combining approaches from biophysics and experimental evolution, he is able to identify and characterize intermediates along the mutational pathways of adaptation and then link those intermediates to the overall evolutionary trajectory of the bacterial populations.  Adaptive changes in protein sequence and expression impact organismal fitness and, consequently, dictate population dynamics.  Dr. Shamoo has been appointed to Rice’s Department of Evolutionary Biology and Ecology and is Director of the Rice Institute of Biosciences and Bioengineering (IBB).  IBB has a large K-12 outreach program as well as a primary role in developing interdisciplinary research. He has won the university-wide George R. Brown Teaching Award for teaching excellence.  He is committed to bringing the strengths of evolutionary biology and biophysics into a new approach that will be truly transformative for our understanding of adaptation.

ASM MEMBERSHIP AFFILIATION

Primary Division        H         Genetics & Molecular Biology