Our group's goal is to characterize genes and molecular pathways that control eye and brain development. We are particularly interested in discovering new molecular networks that modulate cell proliferation and cell death. We can offer you a great research environment at the University of Tennessee Medical School in Memphis, plenty of new space and equipment, and bright job prospects in both basic and applied functional genomics. Our work is currently funded by two R01 grants, two program projects, and a large Center for Excellence in Genomics and Bioinformatics. We can introduce you to:
We are looking for colleagues to collaborate in several broad areas:
All applicants should have a publication history that includes at least two full length papers in print (or in press) in international English language journals.
Pay scale will be at or above NIH scale: between $28,000 and $40,000 depending on background and potential.
If you are an advanced postdoctoral fellow looking for an independent
position and think that your interests would be complementary to what we
are doing, please send us a cv. We are expanding rapidly and will have
several openings in the next year.
A preprint of a paper by L. Lu, D. C. Airey, and R. W. Williams describing new QTLs that modulate size and neuron number in the mouse hippocampus. This paper contains extensive data on hippocampal weight, volume, and cell number as a function of age, sex, and brain weight. We discovered an interesting gain in weight with age that may be related to neurogenesis in the adult mouse hippocampus.
An introduction to mapping quantitative trait loci (QTLs) written for neuroscientists taking the 1998 Short Course in Quantitative Neuroanatomy. Updated August 2000 with new figures and text on RIX mapping.
A review chapter from Mouse Brain Development that explains the power of QTL mapping in exploring CNS development. This review included original data on brain weight and neuron number in different strains of mice (C57BL/6J mice have about 100 million cells in their brains). My thanks to Richelle Strom, Guomin Zhou, and Dan Goldowitz for allowing me to use some of our unpublished data in this review.
A companion to the hippocampus paper above. We describe a set of four QTLs that modulate the weight of the olfactory bulbs. This paper also has lots of data on bulb weight as a function of age, sex, and brain weight. So far, there is no overlap in QTLs that modulate bulb and hippocampus. In press at Behavior Genetics, Aug 2000.
A preprint by David C. Airey and colleagues. This work considers both the overall size of the cerebellum and the fractional volume of different cerebellar compartments. A number of QTLs with relatively intense effects on cerebellar size have been mapped successfully in a cross between C57BL/6J and DBA/2J and in the BXD recombinant inbred strains. The figure below shows the effects of two of these QTLs, singly and jointly, on cerebellar weight in the BXD RI strains.
Release 1 of the BXN RI mapping panel (Jan 15, 2001). This preprint describes a revived resource for mapping complex traits, particularly those that affect CNS structure and behavior. This preprint includes links to new RI genotype data files.
This paper describes a new technique to exploit consomic mice (also known as chromosome substitution strains) to increase the sensitivity of a recessive mutagenesis screen by restricting analysis to entire litters of nearly isogenic mice. The method is sensitive enough to detect QTLs and weak alleles. The consomic mutatgenesis screen is being used by the Tenneessee Mouse Genomics Consortium to generate and map CNS and behavioral mutations on chromosome 19. This paper was published in Mammalian Genome (1999).
A paper on the genetic basis of variation in the eye and retina published in Seminars in Cell & Developmental Biology (1998) 9:249–255. We explain how QTL analysis can be used to detect and characterize genes that modulate the architecture of the eye and retina. We include original data on the genetic control of (1) eye weight, (2) numbers of horizontal cells, and (3) numbers of retinal ganglion cells. This paper was coauthored with Richelle Strom, Guomin Zhou, and Yan Zhen.
An updated and extended version of a paper published in The Journal of Neuroscience (1996). This paper addresses the role of genes and envrionmental factors in controlling the size of cell populations in the central nervous system. Quantitative electron microscopy was used to count neurons in retinas of over 450 animals. We measured effects of sex and age, heritability of differences in neuron populations, and the number of genes responsible for the substantial differences among strains of mice. Updated May 30, 1998.
This paper follows up on the previous article and was published in early 1998 in The Journal of Neuroscience. Our aim in this work was to map genes that produce large differences in numbers of neurons in the retina. We succeeded in mapping a gene locus called Neuron Number Control 1 or Nnc1, on chromosome 11 between Hoxb and Krt1. There are several great candidate genes in this region, particularly the thyroid hormone alpha receptor. Nnc1 is the first gene locus known to control normal variation in neuron number in a vertebrate.
Our third paper in this series on the genetic control of the retinal ganglion cell population in mice. By estimating total cell production in neonates from 10 different inbred strains of mice, Richelle Strom and I were able to determine that the distinct bimodality of strain averages is caused by differences in cell production. This paper demonstrates that Nnc1 modulates cell production and must be expressed before birth. Cell death is comparatively uniform among strains. Published in The Journal of Neuroscience.
Genetics of Eye Size and Myopia
This is a preprint of a paper that explores the genetic basis of variation in the growth of the mouse eye. The print edition was published in Investigative Ophthalmology and Visual Science, April, 1999.
Our aim is to develop mice as a model species for research on myopia. Myopia is casued by a comparatively modest overgrowth of the back part of the eye. We would like to know what genes and molecular mechanisms contribute to eye growth in general, and to the overgrowth of myopia in particular. This paper provide a lot of essential data on the size and growth of the normal mouse eye, lens, and retina. We've included a great deal of information on correlations among several important size parameters. For example, one might expect lens size and eye size to be tightly related in mice, but they are not. The print edition of this paper was published in a special myopia issue of Optometry and Vision Science (1999) 76:408–418..
Background illustration running along the left margin is a drawing of
the apical dendrite of a layer V pyramidal cell in the auditory cortex
of an adult Mongolian gerbil by RWW (Feb 1979). This work is from a
quantitative Golgi analysis of the effects of auditory deprivation on
dendritic spine density (Williams et al., 1979, abstract only).
Background illustration running along the left margin is a drawing of the apical dendrite of a layer V pyramidal cell in the auditory cortex of an adult Mongolian gerbil by RWW (Feb 1979). This work is from a quantitative Golgi analysis of the effects of auditory deprivation on dendritic spine density (Williams et al., 1979, abstract only).
Neurogenetics at University of Tennessee Health Science Center
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