The Faculty in Reproductive Biology at Illinois

David J. Miller

Animal Sciences
Ph.D., University of Wisconsin, Madison

Visit the Miller Lab Group Page

To e-mail Dr. Miller use: d-mille@uiuc.edu

The long-term goal of our research is to develop a more thorough understanding of fertilization that will provide a foundation for the rational development of novel technologies to either 1) promote fertility, by developing more accurate diagnostic and effective therapeutic tools or 2) prevent fertility, by developing more effective contraceptives with fewer side effects. We use animals ranging from mice and frogs to swine and cattle for our experiments.

My laboratory is focused on studying molecular aspects of fertilization. We are investigating how egg coat (zona pellucida) proteins bind sperm and signal sperm to undergo the acrosome reaction. This is mediated by zona receptors on the surface of sperm.  One such receptor is a longer surface form of beta-1,4 –galactosyltransferase-I that activates a cascade of signals in the sperm plasma membrane and cytosol leading to a release of the sperm acrosome. Many of these signaling molecules involved may be similar to those found in somatic cells, including guanine nucleotide binding proteins (G-proteins), tyrosine kinases, and calcium.

There is evidence that other zona receptors allow mammalian gametes to interact. Our goal is to identify those receptors and develop a more complete understanding of gamete interaction. Fertilization appears to be a more complicated process that a single basic ligand-receptor interaction.

Although it has been proposed for years to be carbohydrate, the component of the zona pellucida that binds sperm is controversial. We are currently using a novel approach to identify the element/s of the zona pellucida that bind sperm and then to identify their receptors.

After the zona pellucida binds sperm, it triggers an exocytosis known as the acrosome reaction. This process has some interesting similarities to neuronal secretion but also some intriguing differences.  We are interested in determining how membrane fusion and secretion of this single large vesicle from sperm is accomplished.

Last, we are investigating the steps that are most often defective in males producing low fertility sperm. We have developed a sensitive assay that can be used to detect the defective steps in subfertile sperm. This allows us to systematically screen the most frequent causes of subfertility or infertility in males.

News Items

Researchers isolate proteins that allow sperm to penetrate egg

Selected Publications:

Braundmeier, A.G., Demers, J.M., Shanks, R.D., and Miller, D.J. 2004. The ability of porcine sperm to bind the zona pellucida is related to litter size after insemination.  J Anim Sci,  82(2):452–8. [Abstract]

Burkin, H.R., Alves-Vieira, A.P., and Miller, D.J. 2004. Localization of zona pellucida receptors on live sperm by fluorophore-conjugated solubilized zona pellucida proteins. Meth Molecular Biol.: Germ Cell Protocols, 253:79–93. [No abstract available]

Shi, X., Belton, Jr., R.J., Burkin, H.R., Vieira, A., and Miller, D.J. 2004. A proteomic approach to identify phosphoproteins encoded by cDNA libraries.  Anal Biochem., 329(2):289–92. [Abstract]

Burkin, H., Zhao, L., and Miller, D.J. 2004. CASK is in the mammalian sperm head and is processed during epididymal maturation. Mol Reprod Dev, 68(4):500–6. [Abstract]

Bao, S., Miller, D.J., Ma, A., Wohltmann, M., Eng, G., Ramanadham, S., Moley, K., and Turk, J. 2004. Male mice that do not express group VIA phospholipase A2 produce spermatozoa with impaired motility and have greatly reduced fertility. J Biol Chem, 279(37):38194–200. [Abstract]

Vieira, A. and Miller, D.J. 2006. Gamete interaction: is it species-specific? Mol Reprod Dev, 73(11):1422–9. [PMID: 16894548 PubMed indexed for MEDLINE]

Zhao, L., Shi, X., Li, L., and Miller, D.J. 2006. Dynamin 2 associates with complexins and is found in the acrosomal region of mammalian sperm. Mol Reprod Dev, EPUB ahead of print. http://www3.interscience.wiley.com/cgi-bin/abstract/113489646/ABSTRACT.

View David J. Miller's publications at the National Library of Medicine (PubMed)

Last updated January 9, 2007

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