Ernest Hannig

Associate Professor - Biological Sciences
hannig@utdallas.edu
972-883-2505
FN3106
Tags: Biology

Professional Preparation

Ph.D. - Microbiology and Molecular Genetics
University of Medicine and Dentistry of New Jersey/ Rutgers University - 1985
M.S. - Biology
Seton Hall University - 1979
B.S. - Biology/Medical Technology
Seton Hall University - 1976

Research Areas

Research Interests

Translational Regulation in Yeast

Protein synthesis in eukaryotic organisms is a complex process that requires cooperation among a large number of polypeptides including ribosomal proteins, modification enzymes, and ribosome-associated translation factors. Our research focuses on the initiation phase of protein synthesis, during which ribosomes select mRNAs to be translated and identify the translational start site. This process requires a set of eukaryotic translation initiation factors (eIFs), many of which are comprised of multiple polypeptide subunits (Fig. 1). Initiation factors, as well as the overall pathway for initiation of protein synthesis, appear to be conserved between eukaryotes as widely divergent as yeasts and humans. In fact, a number of yeast initiation factors have been shown to substitute in in vitro initiation reactions using otherwise mammalian components, while a number of mammalian genes encoding initiation factor subunits have been shown to substitute in vivo for their yeast counterparts. Because of the ability to combine powerful genetic approaches with biochemical analyses, we use the yeast Saccharomyces cerevisiae as a model system to dissect the complexities of eukaryotic protein synthesis.

One area of current research is eIF2 and its guanine nucleotide exchange factor eIF2B. eIF2 is a heterotrimeric GTP-binding protein whose known functions include delivery of charged initiator methionyl-tRNA to the ribosome, as well as a role in identifying the translational start site. The three eIF2 subunits are encoded by essential genes (a, SUI2; b, SUI3; g, GCD11). eIF2B is a heteropentamer, and four of the five corresponding structural genes (GCD1, GCD2, GCD6, and GCD7) are essential in yeast.

Although we understand something of the overall function of these two translation factors, less is known about the function of individual subunits within these macromolecular complexes. It is important to identify these functions, particularly since altered regulation of eIF2 and eIF2B function has been shown to result in malignant transformation in mammalian systems.

Earlier work from our lab lead to the initial report describing a structural gene encoding a g-subunit of eIF2, the GCD11 gene in S. cerevisiae. Clues to the function of eIF2g can be found in its deduced amino acid sequence, which bears remarkable similarity to prokaryotic and mitochondrial EF-Tu proteins. EF-Tu binds charged elongator tRNAs in a GTP-dependent fashion, and is the prototypical member of the GTP-binding family of translational factors. The sequence similarity between eIF2g and EF-Tu proteins apparently reflects functional similarities, as genetic and biochemical studies from our lab (Erickson and Hannig, 1996) indicate that the g subunit plays a major role in ligand-binding by eIF2 (i.e., binding guanine nucleotides and charged initiator methionyl-tRNA). Biochemical analysis of additional eIF2 complexes containing alterations in the g subunit (as well as the a and b subunits) may reveal subunit functions that lie downstream from ligand-binding in the initiation pathway.

We are also examining interactions between eIF2 and eIF2B. Considerable interest exists in eIF2B because it is the most complex guanine nucleotide exchange factor currently known. The reasons for this complexity are not clear, but may reflect different catalytic and/or regulatory functions for individual subunits. We recently identified conditions that appear to reduce the requirement for eIF2B in yeast. Analysis of these mutants and additional partial loss-of-function mutations should allow us to address the role(s) of individual subunits in eIF2B function, and thereby gain a more complete understanding of this complex exchange factor.

Publications

Singh, C. R., Curtis, C., Yamamoto, Y., Hall, N. S., Kruse, D. S., He, H., Hannig, E. M., and Asano, K. 2005. e1F5 is critical for integrity of scanning preinitiation complex and accurate control of GCN4 translation. Mol. Cell Biol., 25: 5480-5491. 2005 - Publication
Yamamoto, Y., Singh, C. R., Marintchev, A., Hall, N. S., Hannig, E. M., Wagner, G., and Asano, K. 2005. The e1F5 AA-box domain has two distinct interfaces for multifactor assembly and scanning. Proc.Natl. Acad. Sci. USA, 102: 16164-16169. 2005 - Publication
Asano, K., Phan, L., Krishnamoorthy, T., Pavitt, G.D., Gomez, E., Hannig, E.M., Nika, J., Donahue, T.F., Huang, H.-k., and Hinnebusch, A.G. 2002. Analysis and reconstitution of translation initiation in vitro. Meth. Enzymol., 351, 221-247. 2002 - Publication
Erickson, F.L., Nika, J., Rippel, S., and Hannig, E.M. 2001. Minimum requirements for the function of eukaryotic translation initiation factor 2. Genetics, 158, 123-132. 2001 - Publication
Nika, J., Rippel, S., and Hannig, E.M. 2001. Biochemical analysis of the eIF2 By complex reveals a structural function for eIF2ot in catalyzed nucleotide exchange. J Biol. Chem., 276, 1051-1056. 2001 - Publication
Nika, J., Yang, W., Pavitt, G., Hinnebusch, A.G., and Hannig, E.M. 2000. Purification and kinetic analysis of eIF2B from Saccharomyces cerevisiae. J Biol. Chem., 275, 26011-26017. 2000 - Publication
Astrom, S.U., Nordlund, M., Erickson, F.L., Hannig, E.M. and Bystrom, A.S. 1999. Modification of adenosine 64 of the yeast initiator tRNA is required for optimal tRNAiMet:GTP:e1F -2 ternary complex interactions. Mol. Gen. Genet., 261, 967-976. 1999 - Publication
Huang, H., Yoon, H., Hannig, E.M., and Donahue, T.F. 1997. GTP hydrolysis controls stringent selection of the AUG start codon during translation initiation in Saccharomyces cerevisiae. Genes Devel., 11, 2396-24 1 3 . 1997 - Publication
Erickson, F.L., Harding, L.D., Dorris, D.R., and Hannig, E.M. 1997. Functional analysis of initiation factor 2y homologs. Mol. Gen. Genet. 253, 711-719. 1997 - Publication
Nika, J., Erickson, F.L., and Hannig, E.M. 1997. Ribosomal protein L9 is the product of GRC5, a homolog of the putative tumor suppressor QM in S. cerevisiae. Yeast, 13, 1155-1 166. 1997 - Publication

Appointments

Associate Professor
The University of Texas at Dallas [1996–Present]
Assistant Professor
The University of Texas at Dallas [1990–1996]
Postdoctoral Fellow
NICHHD, NIH, Bethesda, Maryland [1985–1990]
Predoctoral Trainee
Rutgers Medical School [1982–1985]
Medical Technologist (ASCP)
College Hospital/UMDNJ, Newark, New Jersey [1976–1982]
Division of Clinical Microbiology

Additional Information

Professional Activities
  • Member, Genetic Mechanisms of Cancer Study Section, American Cancer Society (1997-2000)
  • Reviewer (grants) (ad hoc), Wellcome Foundation (Great Britain)
  • Reviewer (grants) (ad hoc), National Science Foundation, Molecular Biochemistry Study Section
  • Reviewer (grants) (ad hoc), Austrian Science Foundation (Fonds zur Foderung der wissenschaitlichen Forschung)
  • Reviewer (grants) (ad hoc) K-INBRE Pilot Grant Program
  • Reviewer (journal), Molecular and Cell Biology
  • Reviewer (journal), Molecular and Cellular Biochemistry
  • Reviewer (journal), Molecular Biology and Evolution
  • Reviewer (journal), Gene
  • Reviewer (journal), Genetics
  • Reviewer (journal), Journal of Biological Chemistry
  • Reviewer (textbook) Weaver, R.F. and Hedrick, P.W., Genetics, 3rd edition. Wm. C. Brown, publisher
  • Reviewer (textbook) Lewin, B. Genes VIII. Oxford University Press, publisher
  • Reviewer (textbook) Cappucino, J. G., and Sherman, N. Microbiology: A Laboratory Manual, 7th ed.(8th ed) Benjamin Cummings, publisher
  • Reviewer (textbook) Madigan, M. T. et al. Brock Biology of Microorganisms, 10th ed. Prentice Hall, publisher
  • Reviewer (textbook) Madigan, M. T. et al. Brock Biology of Microorganisms, ll"` ed. Prentice Hall, publisher (published in 2005).
  • Reviewer (textbook) Russell, Peter. iGenetics: a Mendelian Approach. Pearson Benjamin Cummings, San Francisco, publisher (published in 2005).
  • Test Bank Author for Russell, Peter. iGenetics: a Mendelian Approach. Pearson Benjamin Cummings, San Francisco, publisher (published in 2005)
Academic Citizenship
  • Graduate Education Committee (1996-current; Chairman 1996-2000; 2002-current)
  • Institutional Animal Care and Use Committee (IACUC) (1991-94; Chairman 1993-94)
  • Institutional Animal Care and Use Committee (IACUC) (1998-2005; Chairman 1998-2005)
  • Molecular and Cell Biology Faculty Search Committee (1991; 1996; 1998)
  • Molecular and Cell Biology Chairman Search Committee [1994-95; 2000-01(Chairman)]
  • Undergraduate Advisor (1991-current)
  • Undergraduate Education Committee (1994-96)
  • Curriculum coordinator for undergraduate Genetics and Microbiology (2000-current)
  • Health Professions Advisory Committee (1991-current)
  • University Campus Facilities Planning Committee (2003-current)
  • University Library Committee (2001-2003; Vice Chairman 2001-2003)
  • University Safety Committee (Chemical Safety Subcommittee) (1995-98)
Professional Memberships
  • American Society for Biochemistry and Molecular Biology
  • Genetics Society of America

Affiliations

Students Graduated
XioFeng Yang (M.S., May, 1994) Thesis: "Molecular modeling of the y-subunit of eukaryotic initiation factor 2 (elF2) from Saccharomyces cerevisiae". Current position: Postdoctoral Fellow/Research Scientist, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX. David Dorris (Ph.D., August, 1994) Thesis: "Characterization of mutations that alter the function of eIF2y in the yeast Saccharomyces cerevisiae". Current position: Director, RNA Interference Technologies, Ambion, Inc., Austin, TX. F. Les Erickson (Ph.D., December, 1996) Thesis: "Functional analysis of eIF2y and its interactions with ligands and e1F2B". Current position: Assistant Professor, Department of Biological Sciences, Salisbury University, Salisbury, MD. Joseph Nika (Ph.D., August, 1999) Thesis: "Characterization of the eIF2 guanine nucleotide exchange reaction". Current position: Assistant Professor and Health Professions Advisor, University of Nevada at Las Vegas, Las Vegas, NV. Scott Rippel (Ph.D. August, 1999) Thesis: "Analysis of e1F 2 and it role in delivery of Met-tRNAiMet to the correct translational start site". Current position: Senior Lecturer, Department of Molecular and Cell Biology, The University of Texas at Dallas, Richardson, TX.

Funding

Translational Regulation in Yeast
$270,000 - American Cancer Society [1997–2001]
Translational Regulation in Yeast
$60,000 - National Science Foundation [1996–1997]
Molecular and Cell Biology Program, The University of Texas at Dallas
$5,000 - Institutional BRSG [1992–1993]
Translational Regulation in Yeast
$285,000 - National Science Foundation [1991–1995]
Molecular and Cell Biology Program, The University of Texas at Dallas
$28,029 - Institutional BRSG [1990–1991]