Asma Hatoum-Aslan

Asma  Hatoum-Aslan

Assistant Professor


Education

  • Ph.D., Biochemistry, Cornell University, 2007
  • Postdoctoral research: Rockefeller University

Research Interests

Research in the Hatoum-Aslan lab seeks to gain a mechanistic understanding of the perpetual microscopic war that has been raging for billions of years between bacteria and the viruses that attack them. Bacterial viruses, also known as phages, attach to a specific host, inject their DNA, and replicate exponentially while destroying the host. In response, bacteria have evolved a myriad of complex immune systems to fend off invading phages. Our research uses the tools of molecular biology, genetic engineering, bacteriology, and biochemistry to probe and understand the defensive and offensive molecular mechanisms that bacteria and phages use against each other. A second research focus seeks to leverage the antimicrobial properties of phages and genetically engineer them for use in novel therapeutics that will help addresses the global health care crisis incited by the rise in antibiotic-resistant infections. For more information click here. You can also follow us on twitter @crisprcas10

In the long-term, the Hatoum-Aslan lab is also engaged in research that explores novel genome editing technologies and other potential applications for CRISPR-Cas systems.

 

Project 1. Investigating mechanisms of CRISPR-Cas immunity in staphylococci

Funded by NSF (CAREER Award 1749886), NIH (R15GM129671), and NIH (K22 Award AI113106)

 

CRISPR-Cas systems are a class of prokaryotic immune systems that use small CRISPR RNAs (crRNAs) and CRISPR-associated (Cas) proteins to detect and destroy mobile genetic elements such as plasmids and invading phages. CRISPR-Cas systems are remarkably diverse, with two broad classes and six distinct Types currently described. Type III systems are among the most widespread in nature, and likely the most complex. We study a model Type III CRISPR-Cas system in Staphylococcus bacteria, also known as CRISPR-Cas10. Several ongoing projects in the lab carry out pioneering research on CRISPR-Cas10 to understand the complex ways in which it is regulated in the cell, and the extent to which it interacts with and impacts other cellular processes (Walker et al, 2017).

General mechanism of CRISPR-Cas immunity

 

Project 2. Engineering phage-based diagnostics and antimicrobials

Funded by UA start-up funds

 

The evolution of antibiotic resistance in pathogenic bacteria, coupled with the sharp decline in the discovery of new antibiotics, are together responsible for inciting a global public health crisis. Drug-resistant Staphylococcus bacteria are leading causes of healthcare-associated infections. Virulent phages, which kill staphylococci within minutes of infection, represent viable alternatives or supplements to conventional antibiotics. However, phage genomes are replete with genes of undetermined functions which can cause unknown downstream side-effects. In this project, our work aims to help stem regulatory and safety concerns over the use of phages in humans. To achieve this, we developed a platform for genetically engineering virulent phages using CRISPR-Cas10 (Bari et al, 2017), and ongoing work seek to engineer phages with well-defined components that can potentially be used as diagnostic tools and antimicrobials.

 

Project 3. Discovering and characterizing new phages and anti-phage immune systems

Funded by an NSF CAREER Award (1749886) and two UA CARSCA (College Academy of Research, Scholarship, and Creative Activity) Awards

 

Although phages are the most abundant organisms on the planet, with an estimated 1031 particles in the biosphere, a mechanistic understanding of their lifestyles remains in its infancy. Ongoing projects in the lab and in Dr. Hatoum-Aslan’s “Phage Discovery” course seek to discover and characterize new phages that infect known pathogens such as Staphylococcus and Proteus bacteria. Dozens of phages have already been discovered (see Cater et al, 2017 for an example), and the continual expansion of our phage collection is paramount to understanding phage diversity and the diverse immune mechanisms their hosts have evolved to fight back.

Staphylococcus phages discovered in Tuscaloosa, AL Scale bar = 100 nm

Selected Publications

Hatoum-Aslan A. (2018). Phage Genetic Engineering Using CRISPR–Cas Systems. Viruses, 10(6), 335. DOI: 10.3390/v10060335.

Bari SMN, Walker FC, Cater K, Aslan B, and Hatoum-Aslan A. (2017). Strategies for editing virulent staphylococcal phages using CRISPR-Cas10. ACS Synth Biol, DOI: 10.1021/acssynbio.7b00240.

Cater K, Dandu VS, Bari SMN, Lackey K, Everett GFK, and Hatoum-Aslan A. (2017). “A novel Staphylococcus podophage encodes a unique lysin with unusual modular design.” mSphere, 22(2) e00040-17.

Walker FC, Chou-Zheng L, Dunkle JA, and Hatoum-Aslan A. (2017). “Molecular determinants for CRISPR RNA maturation in the Cas10-Csm complex and roles for non-Cas nucleases.” Nucleic Acids Research, 45(4), 2112-23.

Samai P, Pyenson N, Jiang W, Goldberg G, Hatoum-Aslan A, and Marraffini LA. (2015). “Cotranscriptional DNA and RNA cleavage during type III CRISPR-Cas immunity.” Cell, 161(5), 1164-74.

Hatoum-Aslan A and Marraffini, LA. (2014). “Impact of CRISPR immunity on the emergence and virulence of bacterial pathogens.” Curr Opin Microbiol, 17, 82-90.

Hatoum-Aslan A, Maniv I, Samai P, and Marraffini, LA. (2014). “Genetic characterization of anti-plasmid immunity by a Type III-A CRISPR-Cas System.” J Bacteriol, 196(2), 310-7.

Hatoum-Aslan A, Samai P, Maniv I, Jiang W, and Marraffini, LA. (2013). “A ruler protein in a complex for antiviral defense determines the length of small interfering CRISPR RNAs.” J Biol Chem, 288(39), 27888-97.
*Highlighted by: Bucci, M. (2013). “A Measure of RNA.”, Nat Chem Biol, 9(12), 754.

Maniv I, Hatoum-Aslan A, and Marraffini, LA. (2013). “CRISPR decoys: competitive inhibitors of CRISPR immunity.” RNA biology, 10(5), 694-9.

Hatoum-Aslan A, Palmer KL, Gilmore MS, and Marraffini LA. (2013). “Type III CRISPR-Cas systems and roles of CRISPR-Cas in Bacterial Virulence.” In R. Barrangou & J. van der Oost (Eds.), CRISPR-Cas Systems. Springer-Verlag Berlin Heidelberg.

Bikard D, Hatoum-Aslan A, Mucida D, and Marraffini LA (2012). “Prevention of horizontal gene transfer during bacterial infection by CRISPR interference”, Cell Host Microbe, 12(2), 177-86.
*Highlighted by: Weinberger AD, Gilmore AS. (2012). “CRISPR-Cas: To take up DNA or not: That is the question.” Cell Host Microbe, 12(2), 125-6.

Hatoum-Aslan A, Maniv I, and Marraffini, LA (2011). “Mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA) length is measured by a ruler mechanism anchored at the precursor processing site”, Proc Natl Acad Sci U S A, 108(52), 21218-21222.

Hatoum A, Roberts JW (2008). “Prevalence of RNA polymerase stalling at E. coli promoters after open complex formation”, Mol Micro, 68(1), 17-28.
*Highlighted by: Artsimovitch I (2008). “Post-initiation control by the initiation factor sigma”, Mol Micro, 68(1), 1-3.

Shankar S, Hatoum A, and Roberts JW (2007). “A transcription antiterminator constructs a NusA-dependent shield to the emerging transcript”, Mol Cell, 27, 914-927.