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The Australian National University
Eccles Institute of Neuroscience

Keely Bumsted O'Brien

Contact:
keely.bumsted-obrien@anu.edu.au

Research Team

Graduate Students

  • Hie Rin Lee
  • Angeliza Querubin

Collaborations

At ANU

  • Professor Jan Provis
  • Dr. Jan Hemmi
  • Dr. Brendan O'Brien
  • A/Prof. Michael Ibbotson.

Nationally

    Industry
  • Seahorse Australia, Beauty Point, Tasmania has been instrumental in providing animals and lab space for Seahorse visual development project.
  • Montevideo Squab, Carabost, NSW is assisting in the pigeon vision and visual development work.

Internationally

  • Prof. Anita Hendrickson, University of Washington, USA. Investigating the development of the human retina.
  • Dr. Dorothea Schulte, Max Planck Institute for Brain Research, Germany. Area centralis development and cell cycle regulation during development.
  • Dr. Dror Sharon, Department of Ophthalmology, Hadassah-Hebrew University Medical Center Jerusalem, Israel. Development of the pigeon fovea.
  • Dr. Jim VerHoeve, University of Wisconsin. An ERG component of the seahorse project.
  • Prof. Colin Barnstable and Dr. Joyce Tombran-Tink, Department of Neurobiology and Behaviour, Pennsylvania State University. Anti-angiogenic factors in the developing fovea.

Keely Bumsted O'Brien

Chief Investigator

Biography

I completed my PhD at the University of Washington with Professor Anita Hendrickson. My thesis focused on the developmental progression of cone opsin expression in the primate retina and was supported by a competitively awarded a National Eye Institute's Vision Training Grant. At Yale University under the guidance of Dr. Colin Barnstable, I was awarded a prestigious National Research Service Award from the National Eye institute to study early eye tissue compartmentalization. Seeking further training in manipulating biological systems, I moved to Frankfurt, Germany to work with Dr. Dorothea Schulte and Professor Heinz Wassle at the Max Planck Institute for Brain Research. I identified and cloned several novel candidate genes, learnt to alter gene expression and used the chicken which exhibits some characteristics of the human fovea to study these genes. In 2004, I accepted a lectureship position at the University of Auckland. While in Auckland, I obtained five staff research fund grants, two Auckland Medical Research Foundation grants, and Health Research Council grant- all of which were competitively awarded. My laboratory was established at the ANU in late 2007 where I am a Research Fellow with the ARC Centre of Excellence in Vision Science.

Research Interests

In order to understand the disorders of central vision, we must first understand how the location of the fovea is specified and how it comes to be during development. Considerable work has been carried out to describe human and monkey fovea and foveal development by researchers, including me, currently at ANU, which can be viewed as occurring in three phases: (1) specification of the location of the fovea; (2) the differentiation and concentration of central cones and (3) centripetal migration of neurons to form the foveal depression. My laboratory is investigating the molecular mechanisms that specify the location and cellular composition of the fovea during retinal development. We have identified several candidate genes which are spatially restricted either in or out of the developing rod free zone that may play a role in its specification. In order to functionally test these candidates we employ several methods, including viral infection, electroporation, and antisense oligos to alter gene expression in the developing retina. The impact of this manipulation of gene expression is examined by cell fate mapping, in situ hybridization and immunocytochemistry. In order to carry out these experiments we have moved to alternate experimental models that exhibit some characteristics of the human fovea: the seahorse, chicken and pigeon retinas. Retinal development in birds takes place almost entirely in ovo making them accessible to many experimental manipulations otherwise impractical in mammalian species. In addition, we have recently demonstrated that the seahorse, H. abdominalis, and pigeon retinae have many of the characteristics of the human fovea including a rod free zone, high cone density and foveal pit. H. kuda has a rod free zone, but no foveal pit. Examination of the developing pigeon and H. abdominalis seahorse foveae indicates that it is similar to the human with the foveal pit forming late in retinal development and this coincides with an increase in cone density. The functional significance of a fovea or lack thereof in the H. abdominalis vs H. kuda will be determined by measuring the visual acuity of each species.

Recent Publications (since 2003)

  • Hendrickson, A., K Bumsted O'Brien , R Natoli, V Ramamurthy, D Possin, and J Provis. Rod Photoreceptor Differentiation in Fetal and Infant Human Retina. Experimental Eye Research. 2008 (in press). Impact factor: 2.615, Cited Half-life: 7.1
  • Bumsted O'Brien, KM. 'Development of the Foveal Specialization' The Visual Transduction Cascade: Basic and Clinical Principles. Ed. Barnstable and Tombran-Tink. Humana Press, Inc 2008 (in press)
  • O'Brien, B, J Caldwell, G Ehring, K Bumsted O'Brien, S Luo, S Levinson. Tetrodotoxin Resistant Voltage-Gated Sodium Channels Nav1.8 and Nav1.9 are Expressed in the Retina. Journal of Comparative Neurology. 508(6): 940-51, 2008. Impact factor: 3.915, Cited Half-life: >10, Times cited: 0
  • Heine, P, E Dohle, KM Bumsted-O'Brien, D Engelkamp and D Schulte. Evidence for an evolutionary conserved role of homothorax/Meis during vertebrate retina development Meis2. Development. 135(5):805-11, 2008 Impact factor: 7.293, Cited Half-life: 7.3, Times cited: 1
  • Acosta, M, K Bumsted O'Brien, SS Tan, and M Kalloniatis. Analysis of tangentially dispersing cells in the mouse retina. Journal of Comparative Neurology. 506(3):506-23, 2008. Impact factor: 3.915, Cited Half-life: >10, Times cited: 0
  • Schulte, D and KM Bumsted O'Brien. Creating topography: the development of photoreceptor patterns in the vertebrate retina. Brain Research. 1192:151-164, 2008. Impact factor: 2.218, Cited Half-life: >10, Times cited: 1
  • Bumsted O'Brien, K, A Hendrickson, S Haverkamp, R Ahery-Padan and D Schulte. Expression of the homeodomain transcription factor Meis2 in the embryonic and postnatal retina. Journal of Comparative Neurology. 505(1):85-72, 2007. Impact factor: 3.915, Cited Half-life: >10, Times cited: 2
  • Badde A, KM Bumsted O'Brien, and D Schulte. Chick receptor protein tyrosine phosphatase lambda/psi (cRPTPlambda/cRPTPpsi) is dynamically expressed at the midbrain-hindbrain boundary and in the embryonic neural retina. Gene Expression Patterns. 5(6):786-91, 2005 Impact factor: 2.238, Cited Half-life: 3.4, Times cited: 3
  • Bumsted O'Brien, KM, H Cheng, Y Jiang, D Schulte, A Swaroop and AE Hendrickson. The photoreceptor-specific nuclear receptor NR2E3 is specifically expressed in rod precursors and mature rod photoreceptors in human retina. Investigative. Ophthalmology and Visual Science. 45(8):2807-12, 2004 Impact factor: 3.528, Cited Half-life: 6.4, Times cited: 20
  • Bumsted O'Brien, KM, D Schulte and AE Hendrickson. Expression of Photorecepor-associated Molecules During Human Fetal Eye Development. Molecular Vision. 9:401-409, 2003. Impact factor: 2.329, Cited Half-life: 3.5, Times cited: 13