Kelly is director of the Sloan-Kettering Institute at the Memorial Sloan-Kettering Cancer Center, where he oversees a broad research program focused on the causes, diagnosis, and treatment of cancer. Prior to joining Sloan-Kettering in , Dr. After postdoctoral studies at Johns Hopkins, where he determined the DNA sequences recognized by restriction enzymes, he conducted research on animal viruses at the National Institutes of Health as a member of the U. Public Health Service. Kelly was the co-recipient with Bruce Stillman of the Alfred P. Sloan Jr.
Bruce Stillman, Ph. He moved to Cold Spring Harbor Laboratory as a postdoctoral fellow in and has been there ever since. Initially focusing on understanding the replication of DNA tumor viruses in mammalian cells, Dr. Stillman also studied DNA-replication-coupled chromatin assembly and identified proteins required for inheritance of nucleosomes.
He and his colleagues then characterized the structure of chromosomal origins of DNA replication in the budding yeast S. ORC and other proteins load onto chromosomes competent protein complexes of MCM proteins that are used for initiation of DNA replication once the cell commits to cell division and enters S phase. Recently, Dr. Stillman's lab and others have reconstituted pre-RC assembly in vitro with purified proteins and have characterized how the pre-RC is activated by cell cycle-regulated protein kinases.
Surprisingly, in mammalian cells ORC subunits also play roles in both centromere and centrosome activity during mitosis, thereby linking the initiation of DNA replication to processes that ensure accurate chromosome segregation. He did his graduate research — with David Baltimore at MIT, studying poliovirus genome structure and replication. He began to study the genetic pathways controlling developmental timing in the nematode C.
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Robert Horvitz's lab at MIT and continued those studies while on the faculty of Harvard — , Dartmouth — , and the University of Massachusetts Medical School —present. Currently, the chief research interest of the Ambros lab is the roles of microRNA-mediated regulatory pathways in animal development and human disease. Gary Ruvkun is professor of genetics at Harvard Medical School. His lab uses C. Ruvkun is a graduate of UC Berkeley and Harvard. He began to work with C.
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A few years later the Ruvkun lab found the second microRNA gene, let-7 and showed that it is conserved across animal phylogeny. Most of the genes identified in these screens are conserved across eukaryotic phylogeny, suggesting universality of these nucleotide pathways. Some of these components may be developed as drug targets to enhance RNAi in mammals, a technical improvement that may be necessary to elevate a laboratory tool to a therapeutic modality.
The molecular genetic dissection of the insulin pathway has also been important for understanding and treating diabetes, a disease of insulin-signaling deficits.
The new genes of the insulin pathway that have emerged from these studies represent new targets for diabetes drug development. Ulrich Hartl studied medicine at Heidelberg University. After receiving his MD in and his doctoral degree in biochemistry in he moved to the laboratory of Walter Neupert in Munich, where he worked on the mechanism of protein transport into mitochondria, first as a postdoctoral fellow and from to as a research group leader. In he initiated the work on molecular chaperones and demonstrated, collaboratively with A.
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Horwich, the basic role of chaperones in assisting protein folding. After returning to Munich he received his Habilitation in Biochemistry and soon after accepted an offer from Sloan-Kettering Cancer Center in New York to join the newly founded department of James Rothman as an associate member. From to , Dr. Hartl investigated the mechanisms of protein-folding in the bacterial and eukaryotic cytosol. He reconstituted the pathway of chaperone-assisted folding in which the Hsp70 and the GroEL chaperone systems cooperate and discovered that GroEL and its co-factor GroES provide a nano-cage for single protein molecules to fold unimpaired by aggregation.
In Hartl was promoted to member with tenure, and in he became an Investigator of the Howard Hughes Medical Institute. Hartl continues to investigate the mechanisms of cellular protein-folding using a range of methods from cell biology, biochemistry, and structural biology. In addition, he initiated research into neurodegenerative diseases caused by protein misfolding and aggregation.
This work led to the finding that chaperones can effectively inhibit the formation of amyloid aggregates associated with neurodegeneration. Much of this work was done in collaboration with Manajit Hayer-Hartl. Arthur Horwich received undergraduate and medical degrees from Brown University, then trained in pediatric medicine at Yale.
As a postdoctoral fellow at the Salk Institute, he studied transforming T antigens with Walter Eckhart and Tony Hunter, then returned to Yale for further postdoctoral training with Leon Rosenberg. The latter studies were directed to understanding the posttranslational import of mitochondrial precursor proteins, examining signal peptides in the precursor proteins. Following appointment to the Yale faculty in Genetics in , Dr. Horwich focused on the mitochondrial "machinery" that recognizes and translocates precursor proteins.
In a genetic screen in yeast, uncovered Hsp60 the yeast homologue of GroEL as essential for folding newly imported proteins in work in collaboration with Ulrich Hartl. He has been an attending physician in medical genetics and pediatrics at Yale-New Haven Hospital for the past 20 years. Horwich was elected to the National Academy of Sciences in He is an associate editor of Cell and Molecular Cell and a member of the editorial boards of the Journal of Cell Biology and Structure.
Joseph G. Gall received the BS degree in zoology from Yale University in early then directly entered Yale's graduate program zoology.
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He completed his PhD in , working with the Drosophila geneticist and developmental biologist Donald F. He took a teaching position in the zoology department at the University of Minnesota, where he remained until In the fall of he returned to Yale as a visiting professor in what was then the biology department, after the fusion of zoology and botany, and later became professor of biology with a joint appointment in molecular biophysics and biochemistry. Gall remained at Yale for 20 years, from to; during the last few years he held the Ross G.
Harrison Chair in Biology. In he joined the embryology department of the Carnegie Institution in Baltimore as a staff member. Gall has been an active member of the American Society for Cell Biology ASCB since its inception in , serving as president — 68 and as a member of its council and several committees at various times.
Gall's long-term research interests have been in the structure and function of the cell, particularly the nucleus. These are the largest known chromosomes and permit various observations and manipulations that are difficult or impossible with smaller chromosomes.
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Among his more important findings, made at a time when the site of cellular RNA synthesis was still unclear late s, early s , was that cellular RNA synthesis occurs on loops of DNA that extend out from the axis of the chromosome. Studies on the kinetics of DNase digestion showed that the chromosome consists of a single extremely long DNA molecule. Electron microscopic studies he carried out at about the same time on the nuclear envelope established the existence of the nuclear pore complex and its eight-fold symmetry. Other studies on centrioles clarified aspects of their replication during the cell cycle.
After moving to Yale, Dr. In —68, through a combination of biochemical and cytological observations, he demonstrated that these genes are able to leave the chromosome and replicate independently during the early stages of oocyte formation in amphibians and other animals. This phenomenon of gene amplification was independently discovered by Igor Dawid and Donald Brown of the Carnegie Institution. At about the same time, a former postdoctoral student of Dr. The studies on gene amplification were followed almost immediately by development of the technique of in situ hybridization, in collaboration with Dr.
Their original technique used radioactive probes. The procedure was later modified by others to use fluorescent probes, which permit even finer localization and simultaneous use of multiple probes. In situ hybridization is now one of the most widely used cytological techniques.
It permits localization of genes to specific chromosome regions and of RNA sequences to specific cells or groups of cells. Among several important observations Dr. They also showed how in situ hybridization could be used with the giant chromosomes of Diptera for precise gene localization. A few years later, gene cloning made numerous sequences available for mapping studies. Work on this organism led to the demonstration that the rDNA genes exist as free molecules in the macronucleus. A postdoctoral fellow, Elizabeth Blackburn, found that the ends of these molecules had a unique structure consisting of a hexanucleotide repeat GGGGTT.
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Later studies by Blackburn and others established that this repeat, or very similar ones, are found at the ends or telomeres of chromosomes from nearly every type of animal and plant investigated. The in situ hybridization technique was valuable in making this determination. In recent years, the focus of Dr. His lab is concentrating on several nuclear organelles that contain snRNAs, including the nucleolus, Cajal bodies, and nuclear speckles.
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The research findings from Dr. His research has been combined with his long-standing interest in the history of biology, particularly cell biology and microscopy. In , Dr. Gall co-edited with J. Elizabeth H. Blackburn is a leader in the area of telomere and telomerase research, with broad experience in the different aspects of telomere function and biology. She discovered the ribonucleoprotein enzyme, telomerase.
Her laboratory is a leader in manipulating telomerase activity in cells, and she has amassed considerable knowledge and experience in the effects this has on cells. Blackburn and her research team at the University of California, San Francisco, are working with various cells, including human cancer cells, with the goal of understanding telomerase and telomere biology. Her work on telomeres and telomerase has been published extensively in peer-reviewed journals.
She did her postdoctoral work in molecular and cellular biology at Yale from to In , she joined the Department of Microbiology and Immunology at UC San Francisco, where she served as department chair from to She is also a non-resident fellow of the Salk Institute.