Current Project Leaders and Student Researchers
Jesse Cahill, Ph.D.
Spanins are required for outer membrane disruption of Gram-negative hosts by phages. Therefore, the release of phage progeny is dependent on spanins. Rz and Rz1 of phage lambda are the best-studied spanins and recent evidence suggests spanins achieve the final step of lysis by fusion—fusing the inner and outer membrane of the host. A genetic screen identified single missense mutants of the spanin complex that block lysis. These mutations cluster in three regions of the complex, suggesting these regions are important for spanin function. However there were no single missense mutants identified in certain regions of the spanin complex, such as between two predicted alpha helices of Rz. Our hypothesis was that this region functions as a flexible linker, and has no other function (such as interaction or fusion). To test this hypothesis, we replaced a 15 aa stretch in this predicted linker region with Gly-Ser repeats. If specific residues were required in this region for spanin function, we would expect function to be lost. Surprisingly, the spanin complex functioned with an artificial linker replacing ~10% of the residues of this protein. My project will focus on extending and contracting this linker to probe the functional limits of the spanin complex. Additionally, I will be probing other regions of the spanin complex for regions that can tolerate linker substitution.
491 Students under Jesse Cahill (2016- present)
Karthik Chamakura, Ph.D.
Single Gene Lysis Systems
The final step in a bacteriophage infection cycle, lysis and release of progeny virions from the host, requires destruction of the bacterial cell envelope, which in Gram-negative bacteria, includes the cytoplasmic membrane, the cell wall (peptidoglycan), and the outer membrane. For the simple, ubiquitous lytic single-strand RNA and DNA phages, lysis is effected by the expression of a single gene. There are three general classes of these phages: the ssDNA microviruses and two classes of ssRNA phages, the leviviruses and the alloleviruses. By studying how these lysis genes make the host undergo lysis, we expect to advance our understanding of how bacteria synthesize and maintain their cell envelope and thus potentially open the way for developing new antibiotic strategies.
Previously, three different single gene lysis systems identified in the well-studied paradigm phages representing the three phage classes: E of the microvirus fX174, A2 of the allolevivirus Qb, and L of the levivirus MS2. Work in done in the Young lab has shown that A2 and E function as specific inhibitors of enzymes in the pathway for murein precursor biosynthesis, MurA and MraY, respectively. The third prototypic lysis protein L causes lysis by an unknown mechanism and is currently being investigated by my team.
Recently, we discovered a fourth mode of single gene lysis system, the lysis protein LysM from the Escherichia coli phage M. LysM was also shown to target peptidoglycan biosynthesis by inhibiting MurJ, the essential lipid II flippase. This recent discovery raises the possibility that ssRNA phages have evolved proteins that target other essential steps in peptidoglycan biosynthesis and maintenance. Thus, understanding the lysis mechanisms of ssRNA phages might facilitate the discovery of novel targets for antibiotic development.
491 Students under Karthik Chamakura (2016- present)
Former Student Researchers
|Johnson, Bryan||graduate school|
|Shrestha, Ritu||PhD program in Biology, Texas A&M University|
|Kaspar, Justin||PhD program in Interdisciplinary Biomedical Sciences at University of Florida|
|Lessor, Lauren||Research Assistant, CPT program, Texas A&M University|
|Mohan, Sheba||Physician Assistant, DFW|
|Tsau, Joshua||MD program, UT Houston Medical School|
|Dachowski, Michael||MD program, University of Texas Medical School, Houston|
|Herrera, Oscar||Clinical Pathology Laboratories, San Marcos|
|Lawler, Jessica||PhD, Dept. of Biological Chemistry & Molecular Pharmacology, Harvard Medical School|
|Migl, David||PhD program in Biophysics, Harvard University|
|Brahmbhatt, Kirtan||MD program, Texas A&M University Health Science Center|
|Kulkarni, Aneesha||PhD program in Molecular Biology focusing in immunology, San Jose State University|
|Park, Katherine||MD program, Baylor College of Medicine|
|Rasche, Eric||Programmer II , CPT program, Texas A&M University|
|Simpson, Jacob||MS Health Administration TAMU HSC|
|Edwards, Garrett||PhD program in Biochemistry, University of Colorado, Boulder|
|Khatemi, Brontee||the director of education at Sylvian Learning Center, Dallas, TX|
|Ladzekpo, Tsonyake||Medical Scribe at PhysAssist Scribes, Inc., Houston, TX|
|Luna, Adrian||PhD program in Biomedical Sciences, University of New Mexico|
|Snowden, Jeffrey||PhD program in Micro-logy & Cell Biology, University of Texas Medical Branch, Galveston|
|Church, Kaira||certification in Clinic Lab, UT Health Science Center in San Antonio, TX|
|Lancaster, Jacob||Research, Texas A&M University|
|Bernal, Christopher||Masters program in BIMS, Texas A&M|
|LeSage, Kayla||Masters program in BIMS, Texas A&M|
|Mijalis, Eleni||MD program at Louisiana State University – Shreveport|
|Crosby, Stephen||PhD program|
|Maughmer, Cory||Software Developer, CPT|