skip navigation

S M L Text size
Home » Research at NEI » Section on Molecular Structure and Functional Genomics

Section on Molecular Structure and Functional Genomics

On this page:

Current Research

A major emphasis of this group is to move beyond single gene, single technology studies in an attempt to integrate genomics, structure and function and evolutionary perspectives to obtain a wider systems view of the molecular biology of the eye. We have made extensive use of genomics and bioinformatics (largely through NEIBank) to gain new insights into the molecular composition of the eye and to identify sets of specific changes in sequence and expression that distinguish the human (and other primate) eye from those of other mammals, opening the possibility of improving animal models of human eye disease. We are now applying the tools of functional genomics to these discoveries, using techniques including yeast 2-hybrid analysis and knock-out/knock-in mouse models to delineate the roles of key proteins. We also pursue direct biophysical studies of recombinant proteins of interest through collaborations with structural biology labs.

NEIBank and Functional Genomics

NEIBank is project for producing, organizing and disseminating genomics resources and expression and sequence data for eye research. The web site is at Collaborators from a wide range of institutions have contributed freshly dissected tissues for cDNA libraries of many eye tissues from many species. These are used for high throughput sequencing. Analyzed data are displayed in the web site, submitted to GenBank and described in peer-reviewed publications. Clones are made available through OpenBiosystems. Eye-related data from other sources are also gathered and displayed through the web site.

Recent additions to NEIBank include:

The data from NEIBank are a rich source for gene discovery and for insights into species and tissue comparisons. Recent examples of this include the following:

Crystallins and the Lens Crystallins are the major structural proteins of the eye lens. They are involved in cataract, which is still a major cause of vision loss world wide, and are fascinating models for processes of molecular evolution and protein interaction. [See: Wistow, G. (1993) Lens crystallins: Gene Recruitment and Evolutionary Dynamism. Trends. Biochem. Sci. 18, 301-306; PubMed ]

Wistow, G. (1995) Molecular Biology and Evolution of Crystallins: Gene Recruitment and Multifunctional Proteins in the Eye Lens. Molecular Biology Intelligence Unit, R.G. Landes Co., Austin TX and Springer, New York.] Recent observations have also implicated ß - and gamma-crystallins in retina and retinal pigment epithelium aging and disease.

We have long standing interests in the genomics, expression, structure and function of crystallins, including collaborative projects for x-ray and NMR structure analyses. Recent work has focused on the analysis of crystallin mutations in cataract and the effects of these mutations as well as differences amongst wild type proteins on stability and solubility. A knock out mouse model is providing new insights into the functional role of gammaS-crystallin both in lens and in the retina/RPE.

Other proteins with key roles in the lens have been identified through the NEIBank project. Of particular interest are:

Recent Publications

Hobby P., Wyatt M.K., Gan W., Bernstein S., Tomarev, S., Slingsby C. and Wistow G. (2000) A Novel Leucine-rich Repeat Protein Expressed in Human Eye: Cloning, Modeling and Chromosomal Localization. Molecular Vision 6, 72-78. PubMed

Wistow, G., Sardarian L., Gan, W. and Wyatt, M.K. (2000) The Human Gene for gammaS-crystallin: Alternative Transcripts and Expressed Sequences from the First Intron. Molecular Vision 6, 79-84. PubMed

Francis, P., Chung, J.-J., Yasui, M., Berry, V., Moore, A., Wyatt, M. K., Wistow, G., Bhattacharya, S. and Agre, P. (2000). Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. Hum Mol Genet 9: 2329-2334 PubMed

Bork, J.M., Peters, L.M., Riazuddin, S., Bernstein, S.L., Ahmed, Z.M., Ness, S.L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C.R.S., Wayne, S., Bellman, S., Desmukh, D., Ahmed, Z., Khan, S.N., Der Kaloustian, V.M., Li, X.C., Lalwani, A., Riazuddin, S., Bitner-Glindzicz, M., Nance, W.E., Liu, X.-Z., Wistow, G., Smith, R.J.H., Griffith, A.J., Wilcox, E.R., Friedman, T.B., and Morell, R.J. (2001) . Usher syndrome 1D (USH1D) and nonsyndromic recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Amer. J. Human Genet. 68:26-37. PubMed

Sinha, D., Wyatt, M. K., Sarra, R., Jaworski, C., Slingsby, C., Thaung, C., Pannell, L., Robison, W. G., Favor, J., Lyon, M. and Wistow, G. (2001). A temperature-sensitive mutation of Crygs in the murine Opj cataract. J Biol Chem 276(12): 9308-15. PubMed

Wistow G., (2002) A project for ocular bioinformatics: NEIBank.Mol. Vis. 8:161-163 PubMed

Wistow G, Bernstein SL, Touchman JW, Bouffard G, Wyatt MK, Peterson K, Behal, A., Gao J, Gesuwan P, Smith D. (2002) Grouping and identification of sequence tags (GRIST): Bioinformatics tools for the NEIBank database. Mol Vis. 8:164-170 PubMed

Wistow G, Bernstein SL, Wyatt MK, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K. (2002) NEIBank: Expressed Sequence Tag analysis of adult human lens for the NEIBank project: Over 2000 Unique transcripts, novel genes and splice variants. Mol Vis. 8:171-184 PubMed

Wistow G, Bernstein SL, Ray S, Wyatt MK, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K. (2002) NEIBANK: Expressed sequence tag analysis of adult human iris for the NEIBank Project: Steroid-response factors and similarities with retinal pigment epithelium. Mol Vis. 8:185-195 PubMed

Wistow G, Bernstein SL, Wyatt MK, Ray S, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K. (2002) Expressed sequence tag analysis of human retina for the NEIBank Project: Retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts. Mol Vis. 8:196-204 PubMed

Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K. (2002) Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: Over 6000 non-redundant transcripts, novel genes and splice variants. Mol Vis. 8:205-220 PubMed

Rajini, B., Graham, C., Wistow G. and Sharma Y. (2003). Stability, homodimerization and calcium-binding of a single, variant ßgamma-crystallin domain of Absent in Melanoma 1 (AIM1). Biochemistry 42:4552-4559. PubMed

Tomarev, S. Wistow, G., Raymond, V., Dubois, S., Malyukova, I. (2003). NEIBank: Gene Expression Profile of the Human Trabecular Meshwork. Invest. Ophthalmol. Vis. Sci. 44:2588-2596. PubMed

Bateman, O., Purkiss, A., van Montfort, R., Slingsby, C., Graham, C. and Wistow, G. (2003)The x-ray structure of  -crystallin: adaptation of a class 1 aldehyde dehydrogenase for a new role in the eye lens. Biochemistry 42:4349-4356. PubMed

Ochrietor,J.D., Moroz, T.P., van Ekeris, L., Clamp, M.F., Jefferson, S.C., deCarvalho, A.C., Fadool, J.M., Wistow, G.J., Muramatsu, T. and Linser, P.J. (2003). Retina expression of 5A11/Basigin-2, a new member of the immunoglobulin superfamily. Invest. Ophthalmol. Vis. Sci. 44:4086-96. PubMed

Wallace, B.A., Wien, F., Miles, A.J., Lees, J.G., Evans, P., Wistow, G.J., and Slingsby, C. (2004). Biomedical applications of synchrotron radiation circular dichroism spectroscopy: Identification of mutant proteins associated with disease and development of a reference database for fold motifs.Faraday Discuss. 126:237 - 243. PubMed

Pompeia C., Hurle, B., Belyantseva, I.A., Noben_Thrauth, K., Beisel, K., Gao, J., Buchoff, P., Wistow, G. and Kachar, B. (2004). Gene Expression Profile of the Mouse Organ of Corti at the Onset of Hearing. Genomics 83:1000-11. PubMed

Ida, H., Boylan, S.A., Weigel, A.L. McBride, Z., Chao, A., Gao, J., Buchoff, P., Wistow, G. and Hjelmeland, L.M. (2004). EST analysis for mouse retina and RPE/choroid cDNA libraries. Mol. Vis. 10:439-444. PubMed

Ahmed, F., Torrado, M., Senatorov, V., Zinovieva, R., Wistow, G. and Tomarev, S. (2004) Gene Expression Profile of the Rat Eye Irido-Corneal Angle: NEIBank Sequence Tag Analysis. Invest. Ophthalmol. Vis. Sci. 45:3081-90 PubMed

Evans, P., Wyatt. M.K., Wistow, G.J., Bateman, O.A., Wallace, B.A. and Slingsby, C. (2004). The P23T cataract mutation causes loss of solubility of folded gammaD-crystallin. J. Mol. Biol. 343:435-44. PubMed

Ray, S., Gao, C., Wyatt, M.K., Fariss, R.N., Bundek, A., Zelenka, P. and Wistow, G. (2005). PDGF-D: Tissue-specific expression in the eye and a key role in control of lens epithelial cell proliferation. J Biol Chem. 280(9):8494-502 PubMed

Fan, J., Fariss, R., Purkiss, A., Quinlan, R., Slingsby, C., Wistow, G. and Chepelinsky, A. (2005). Specific Interaction between lens MIP/Aquaporin-0 and two members of the gamma-crystallin family. Mol. Vis. 11:76-87. PubMed

Rabinowitz, Y., Dong, L. and Wistow, G. (2005). Gene expression profile studies of human Keratoconus cornea for NEIBank: A novel gene and the absence of transcripts for Aquaporin 5. Invest. Ophthalmol. Vis. Sci. 46: 1239-1246. PubMed

Ozyildirim, A.M., Wistow, G. J., Gao, J., Wang, J., Dickinson, D.P., Frierson, H. F. and Laurie, G.W. (2005). The Lacrimal Gland Transcriptome is an Unusually Rich Source of Rare and Poorly Characterized Gene Transcripts. Invest. Ophthalmol. Vis. Sci. 46:1572-80. PubMed

Wistow, G., Wyatt, K., David, L., Gao, C., Bateman, O., Bernstein, S., Tomarev, S., Slingsby, C., Segovia, L and Vihtelic, T. (2005) gammaN-crystallin and the evolution of the
ßgamma-crystallin family in vertebrates. FEBS J. 272: 2276-2291. PubMed

Wu, Z., Delaglio, F., Wyatt, K., Wistow, G. and Bax, A. (2005). Solution structure of gammaS crystallin by molecular fragment replacement NMR. Prot. Sci. 14: 3101-3114 PubMed

Vihtelic, T.S. Fadool, J.M., Gao, J., Thornton, K.A., Hyde, D.R. and Wistow, G. (2005). Expressed sequence tag analysis of zebrafish eye tissues for NEIBank. Mol. Vis. 11:1083-1100. PubMed

Wistow, G. (2006).The NEIBank Project for Ocular Genomics. Data-mining gene expression in human and rodent eye tissues. Prog. Ret. Eye Res. 25(1):43-77. PubMed

Smith, A.A., Wyatt, K., Vacha, J., Vihtelic, T.S., Zigler, J.S., Jr., Wistow, G. and Posner, M. (2006). Gene duplication and separation of functions in B-crystallin in the zebrafish (Danio rerio). FEBS J. 273:481-90. PubMed

Rickman, C.B., Ebright, J.N., Zavodni, Z.J., Yu, L., Wang, T., Daiger, S.P., Wistow, G., Boon, K. and Hauser, M.A. (2006). Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes using EyeSAGE. Invest. Ophthalmol. Vis. Sci. 47:2305-16. PubMed

Wyatt, K., White, H.E., Wang, L., Bateman, O., Slingsby, C., Orlova, E. and Wistow, G. (2006). Lengsin is a survivor of an ancient family of class I glutamine synthetases re-engineered by evolution for a role in the vertebrate lens Structure. 14:1823-34. PubMed

Nag, N., Ray, S., Wyatt, K., Bogani, D., Favor, J., Lyon, M. and Wistow, G. (2007). The murine No3 cataract is the result of endogenous retroviral insertion in cryge. [Genomics. 2007 Epub ahead of print]. PubMed


Name Title E-mail Phone
Graeme J. Wistow Ph.D.
PubMed Aurhor Search
Section Head 301-402-3452
Katherine Peterson Ph.D. Staff Fellow 301-402-3452
Jianguo Fan Ph.D. Staff Fellow 301-402-4812
Nabanita Nag B.Sc. Technical IRTA Fellow 301-402-5351
Sugata Ray Ph.D. Contractor 301-402-3453
M. Keith Wyatt Ph.D. Contractor 301-402-8649
James Gao Ph.D. Contract Programmer 301-402-6369
Patee Buchoff M.Sc. Contract Programmer 301-402-6365


Bookmark or share this page

This page was last modified in October 2008

U. S. Department of Health and Human Services

National Institutes of Health