Frank Grosveld | |
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Born | 18 August 1948 |
Alma mater | University of Amsterdam McGill University |
Awards | Louis-Jeantet Prize for Medicine (1991) [1] Spinoza Prize (1995) [2] |
Scientific career | |
Fields | Molecular biology |
Institutions | Erasmus University Rotterdam |
Franklin Gerardus "Frank" Grosveld, FRS (born 18 August 1948) [3] is a Dutch molecular biologist whose research interests are in the regulation of transcription during development with a particular emphasis on mammalian erythroid differentiation. He is a professor and former Head of the Department of Cell Biology at the Erasmus MC, Rotterdam.
He obtained his PhD degree from McGill University, Montreal and after completing two postdoctoral periods with Charles Weissmann (Zurich) and Richard Flavell (Amsterdam and London) he started his own research group at the National Institute for Medical Research, Mill Hill.
Grosveld has been conducting research on the regulation of gene expression over thirty years. In his post-doctoral research he constructed the first reliable method for cloning human DNA cosmids - at the time an extremely difficult but rewarding accomplishment that has since been adopted by many other laboratories. By using the globin gene cluster he made the ground-breaking discovery of a locus control region located upstream of the gene itself and governing overall control of globin gene expression. After this first report, locus control regions have now been identified for many genes and have permitted for example the ectopic expression of genes in transgenic mice. In further studies he identified chromatin loops and the hubs that hold the loops together. His more recent excursions into erythroid differentiation have made the key identification of the transcription factor GATA1, a major and unique advance into understanding erythroid cell development. Along with major research advances he has also developed new technologies, such as 4C technology (a modification of the 3C technology invented previously by others) that makes possible examination of chromatin conformation on a chip and constructed a number of spin off companies. He has mentored a large number of PhDs and postdocs, many of whom have gone on to academic positions all over the world and are now eminent scientists leading groups of their own. [4]
Grosveld's research on the control of globin gene expression has been selected as one of the top ten achievements of Medical Research Council (UK) (MRC) in the 20th century by Higher Education and Research Opportunities in the UK. [5] He was awarded the Louis-Jeantet Prize for Medicine (1991) and the Spinozapremie (Spinoza Prize) (1995). [6] He was selected as academy professor of Royal Netherlands Academy of Arts and Sciences in 2008. [4]
He is a Fellow of the Royal Society (FRS) and Member of the Royal Netherlands Academy of Arts and Sciences since 1994. [7] [8]
Pierre Chambon was the founder of the Institute for Genetics and Cellular and Molecular Biology in Strasbourg, France. He was one of the leading molecular biologists who utilized gene cloning and sequencing technology to first decipher the structure of eukaryotic genes and their modes of regulation. His major contributions to science include the identification of RNA polymerase II (B), the identification of transcriptional control elements, the cloning and dissection of nuclear hormone receptors, revealing their structure and showing how they contribute to human physiology. His group was also one of the first to demonstrate, biochemically and electron-microscopically, that the nucleosome is the smallest unit of chromatin. He accomplished much of his work in the 1970s – 1990s.
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An insulator is a type of cis-regulatory element known as a long-range regulatory element. Found in multicellular eukaryotes and working over distances from the promoter element of the target gene, an insulator is typically 300 bp to 2000 bp in length. Insulators contain clustered binding sites for sequence specific DNA-binding proteins and mediate intra- and inter-chromosomal interactions.
A locus control region (LCR) is a long-range cis-regulatory element that enhances expression of linked genes at distal chromatin sites. It functions in a copy number-dependent manner and is tissue-specific, as seen in the selective expression of β-globin genes in erythroid cells. Expression levels of genes can be modified by the LCR and gene-proximal elements, such as promoters, enhancers, and silencers. The LCR functions by recruiting chromatin-modifying, coactivator, and transcription complexes. Its sequence is conserved in many vertebrates, and conservation of specific sites may suggest importance in function. It has been compared to a super-enhancer as both perform long-range cis regulation via recruitment of the transcription complex.
The human β-globin locus is composed of five genes located on a short region of chromosome 11, responsible for the creation of the beta parts of the oxygen transport protein Haemoglobin. This locus contains not only the beta globin gene but also delta, gamma-A, gamma-G, and epsilon globin. Expression of all of these genes is controlled by single locus control region (LCR), and the genes are differentially expressed throughout development.
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a transcription factor that is necessary for the proper maturation of erythroid cells.
Krüppel-like Factor 2 (KLF2), also known as lung Krüppel-like Factor (LKLF), is a protein that in humans is encoded by the KLF2 gene on chromosome 19. It is in the Krüppel-like factor family of zinc finger transcription factors, and it has been implicated in a variety of biochemical processes in the human body, including lung development, embryonic erythropoiesis, epithelial integrity, T-cell viability, and adipogenesis.
Transcription factor NF-E2 45 kDa subunit is a protein that in humans is encoded by the NFE2 gene.
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