How do babies get the right numbers of healthy chromosomes from Mom and from Dad?
Chromosomes are long sections of DNA that reside in the nucleus of every cell in the body. Human cells have 46 chromosomes and, when a cell divides to make two new cells, each chromosome duplicates with one copy going to each new cell in order to maintain this normal chromosome number.
One exception to the rule of equal division happens on the way to making sperm and egg cells. In order for babies to have the right number of chromosomes, each of these cells must have only 23 chromosomes, so that the proper number of 46 is restored when the sperm and egg combine to make an embryo. Unfortunately, this process frequently misbehaves and generates damaged or wrong numbers of chromosomes, problems that can lead to Down syndrome, birth defects and genetic diseases.
In my lab, we want to understand how the chromosome number is reduced from 46 to 23, in order to understand what can, and does, go wrong. The way this reduction occurs is remarkably similar in most organisms, including humans, birds, bees, flowers, and even yeast. So, we use yeast as a “model” organism for our experiments because this is the fastest way to discover the critical parts of the reduction process.
It has long been known that the reduction process starts when each of the 23 chromosomes that originally came from Mom finds and joins with its partner among the chromosomes from Dad. Recently, we have discovered an important new part of how this works. Surprisingly (to us), the ends of each chromosome connects to motors that tug the chromosomes quickly around the inside of the nucleus, helping the correct partners to bump into and recognize each other, but also helping to pull apart chromosomes that should not be partners—sort of like meddlesome chaperones at a middle school dance.
Our next goal is to identify the motors and what controls the movements to further study their roles in preventing chromosomal defects and to identify genetic or environmental factors that might interfere with them. The more we know about how those defects occur, the more likely it is that we can pinpoint ways to prevent them from happening.
Education
B.A., Duke University, 1975
M.D., Duke University Medical Center, 1985
Ph.D., Duke University, 1985
Honors and Awards
1973 Phi Lambda Upsilon (Chemistry Honor Society)
1974 Phi Beta Kappa
1975 Strickland Memorial Scholarship, Duke Medical School
1975 Graduate Summa cum laude, Duke University
1978 A.O.A. (Medical Honor Society)
1978 Medical Scientist Training Program Award
1980 Ruska Award (Southeastern Electron Microscopists)
1983 Sigma Xi, Full member
1986 National Research Council Associateship Award
1991 American Cancer Society Junior Faculty Research Award
1998 Edward L. and Thelma Gaylord Prize for Scientific Achievement
Memberships
Genetics Society of America
American Association for the Advancement of Science
American Society for Microbiology
Joined OMRF Scientific Staff in 1989.
Chromosome abnormalities that arise during the development of sperm and eggs can cause infertility, birth defects and increased predisposition to cancer. To prevent these abnormalities, chromosomes of each pair must recognize one another, move together, align closely, exchange parts and then segregate away from one another during meiosis to form the reduced genome of sperm and eggs, thus preparing the genome for the next generation. My laboratory uses the yeast Saccharomyces cerevisiae to identify the molecular mechanisms that carry out these activities.
Our major focus at present is to understand the contribution of telomeres to these processes. Telomeres are structures that stabilize the ends of chromosomes and play roles in aging and prevention of cancer. During meiosis, telomeres draw all chromosomes into a single cluster that persists for a short time, just when chromosome pairs are becoming closely aligned. This event occurs in humans, plants, amphibians, yeast and other organisms, but its purpose remains unexplained. Recently, we have discovered that telomeres tug chromosomes rapidly around the nuclear envelope throughout meiosis, and our analyses indicate that by understanding these movements we will gain insights into currently unknown, fundamental cellular mechanisms that preserve the genome.
We first discovered that Ndj1p is a telomere protein which appears only in meiosis. When Ndj1p is defective, telomeres fail to form the cluster, the movements are slowed, chromosomes are slow to align and chromosomes missegregate, leading to aneuploidy of the sort that causes infertility and birth defects. Using an approach that combines genetics, molecular genetics and high-resolution fluorescence and electron microscopy, we have identified new proteins required to make the cluster, including Mps3p and Csm4p which also localize to telomeres in meiosis. Mps3p is a member of a family of proteins implicated in chromosome and nucleus positioning in various organisms, supporting the idea that the molecular mechanisms we are uncovering are fundamental and widespread.
We have developed and patented new methods of microscopy to track movements in live cells and have found that the telomere-promoted movements are more important than telomere clustering in generating proper chromosome pairing and segregation, providing a new perspective on how the genome is preserved for delivery across generations.
Recent Publications
Havens KA, Gardner MK, Kamieniecki RJ, Dresser ME, Dawson DS. Slk19 of Saccharomyces cerevisiae regulates anaphase spindle dynamics through two independent mechanisms. Genetics 186:1247-1260, 2010.[Abstract]
Dresser ME. Time-lapse fluorescence microscopy of Saccharomyces cerevisiae in meiosis. Methods Mol Biol 558:65-79, 2009. [Abstract]
Dresser ME. Chromosome mechanics and meiotic engine maintenance. PLoS Genet 4:e1000210, 2008. [Abstract]
Selected Publications
Havens KA, Gardner MK, Kamieniecki RJ, Dresser ME, Dawson DS. Slk19 of Saccharomyces cerevisiae regulates anaphase spindle dynamics through two independent mechanisms. Genetics 186:1247-1260, 2010. [Abstract]
Conrad MN, Lee CY, Chao G, Shinohara M, Kosaka H, Shinohara A, Conchello JA, Dresser ME. Rapid telomere movement in meiotic prophase is promoted by NDJ1, MPS3, and CSM4 and is modulated by recombination. Cell 133:1175-1187, 2008. [Abstract]
Conchello JA, Dresser ME. Extended depth-of-focus microscopy via constrained deconvolution. J Biomed Optics 12:1-7, 2007.
Kateneva AV, Konovchenko AA, Guacci V, Dresser ME. Recombination protein Tid1p controls resolution of cohesin-dependent linkages in meiosis in Saccharomyces cerevisiae. J Cell Biol 171:241-253, 2005. [Abstract]
Trelles-Sticken E, Dresser ME, and Scherthan H. Meiotic telomere protein Ndj1p is required for meiosis-specific telomere distribution, bouquet formation and efficient homologue pairing. J.Cell Biol. 151: 95-106, 2000. [Abstract]
Conrad MN, Dominguez AM, and Dresser ME. Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast. Science 276: 1252-1255, 1997. [Abstract]
Cell Cycle and Cancer Biology Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7682
Fax: (405) 271-7312
E-mail: dresserm@omrf.org
Mike Conrad, Ph.D.
Research Associate Member
Chih-Ying “Emma” Lee, Ph.D.
Associate Research Scientist
Robin Harris
Research Assistant
Rachel Evans
Laboratory Technician
Gene Chao
Network Support Specialist
Gerry McElroy
Laboratory Assistant
