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- Creators: Arizona Board of Regents
- Status: Published
I have developed protocols to generate 3D cultures of neurons from hiPSCs and hESCs, to provide more accurate models of AD. In the first protocol, hiPSC-derived neural progenitor cells (hNPCs) are plated in a suspension of Matrigel™ prior to terminal differentiation of neurons. In the second protocol, hiPSCs are forced into aggregates called embryoid bodies (EBs) in suspension culture and subsequently directed to the neural lineage through dual SMAD inhibition. Culture conditions are then changed to expand putative hNPC populations and finally differentiated to neuronal spheroids through activation of the tyrosine kinase pathway. The gene expression profiles of the 3D hiPSC-derived neural cultures were compared to fetal brain RNA. Our analysis has revealed that 3D neuronal cultures express high levels of mature pan-neuronal markers (e.g. MAP2, β3T) and neural transmitter subtype specific markers. The 3D neuronal spheroids also showed signs of neural patterning, similar to that observed during embryonic development. These 3D culture systems should provide a platform to probe disease mechanisms of AD and enable to generation of more advanced therapeutics.
Rosalind Elsie Franklin worked with X-ray crystallography at King's College London, UK, and she helped determine the helical structure of DNA in the early 1950s. Franklin's research helped establish molecular genetics, a field that investigates how heredity works on the molecular level. The discovery of the structure of DNA also made future research possible into the molecular basis of embryonic development, genetic disorders, and gene manipulation.
The General Embryological Information Service (GEIS) was an annual report published by the Hubrecht Laboratory in Utrecht, The Netherlands from 1949 to 1981 that disseminated contemporary research information to developmental biologists. The purpose of the annual report was to catalog the names, addresses, and associated research of every developmental biologist in the world. Pieter Nieuwkoop edited each issue from 1949 until 1964, when Job Faber began assisting Nieuwkoop. Bert Z. Salome joined the editing team in 1968 before Nieuwkoop ceased editing duties in 1971. Faber and Salome remained the editors from 1971 until the periodical's final year of circulation in 1981. The Hubrecht Laboratory, a national laboratory created to house a large collection of comparative embryological materials and loan them to interested researchers, sponsored the publication after World War II to facilitate international collaboration and prevent unnecessary duplication of work. The catalog of researchers and the scientific topics grew in number and variety as the field of developmental biology changed during the publication's thirty-two year history.
Golden Rice was engineered from normal rice by Ingo Potrykus and Peter Beyer in the 1990s to help improve human health. Golden Rice has an engineered multi-gene biochemical pathway in its genome. This pathway produces beta-carotene, a molecule that becomes vitamin A when metabolized by humans. Ingo Potrykus worked at the Swiss Federal Institute of Technology in Zurich, Switzerland, and Peter Beyer worked at University of Freiburg, in Freiburg, Germany. The US Rockefeller Foundation supported their collaboration. The scientists and their collaborators first succeeded in expressing beta-carotene in rice in 1999, and they published the results in 2000. Since then, scientists have improved Golden Rice through laboratory and field trials, but as of 2013 no countries have grown it commercially. Golden Rice is a technology that intersects scientific and ethical debates that extend beyond a grain of rice.
Charles Robert Cantor helped sequence the human genome, and he developed methods to non-invasively determine the genes in human fetuses. Cantor worked in the US during the twentieth and twenty-first centuries. His early research focused on oligonucleotides, small molecules of DNA or RNA. That research enabled the development of a technique that Cantor subsequently used to describe nucleotide sequences of DNA, a process called sequencing, in humans. Cantor was the principal scientist for the Human Genome Project, for which scientists sequenced the entirety of the human genome in 2003. Afterwards, Cantor became the chief scientific officer for Sequenom Inc., a company that provided non-invasive prenatal genetic testing. Such tests use a pregnant woman's blood to identify genetic mutations in a fetus during the first trimester of pregnancy.
George Wells Beadle and Edward Lawrie Tatum's 1941 article Genetic Control of Biochemical Reactions in Neurospora detailed their experiments on how genes regulated chemical reactions, and how the chemical reactions in turn affected development in the organism. Beadle and Tatum experimented on Neurospora, a type of bread mold, and they concluded that mutations to genes affected the enzymes of organisms, a result that biologists later generalized to proteins, not just enzymes. Beadle and Tatum's experiments provided an early link between genetics and the field of molecular biology.
Sir John Bertrand Gurdon further developed nuclear transplantation, the technique used to clone organisms and to create stem cells, while working in Britain in the second half of the twentieth century. Gurdon's research built on the work of Thomas King and Robert Briggs in the United States, who in 1952 published findings that indicated that scientists could take a nucleus from an early embryonic cell and successfully transfer it into an unfertilized and enucleated egg cell. Briggs and King also concluded that a nucleus taken from an adult cell and similarly inserted into an unfertilized enucleated egg cell could not produce normal development. In 1962, however, Gurdon published results that indicated otherwise. While Briggs and King worked with Rana pipiens frogs, Gurdon used the faster-growing species Xenopus laevis to show that nuclei from specialized cells still held the potential to be any cell despite its specialization. In 2012, the Nobel Prize Committee awarded Gurdon and Shinya Yamanaka its prize in physiology and medicine for for their work on cloning and pluripotent stem cells.
Telomerase is an enzyme that regulates the lengths of telomeres in the cells of many organisms, and in humans it begins to function int the early stages of embryonic development. Telomeres are repetitive sequences of DNA on the ends of chromosomes that protect chromosomes from sticking to each other or tangling. In 1989, Gregg Morin found that telomerase was present in human cells. In 1996, Woodring Wright and his team examined human embryonic cells and found that telomerase was active in them. Scientists manipulate telomerase in cells to give cells the capacity to replicate infinitely. Telomerase is also necessary for stem cells to replicate themselves and to develop into more specialized cells in embryos and fetuses.
Francis Harry Compton Crick, who co-discovered the structure of deoxyribonucleic acid (DNA) in 1953 in Cambridge, England, also developed The Central Dogma of Molecular Biology, and further clarified the relationship between nucleotides and protein synthesis. Crick received the Nobel Prize in Physiology or Medicine that he shared with James Watson and Maurice Wilkins in 1962 for their discovery of the molecular structure of DNA. Crick's results on the genetic material found in all living organisms advanced theories of inheritance and spurred further studies into the field of genetics and embryology.