Biography of Vernon M. Ingram. Inside the brains of Alzheimer's patients, tangles of a misfolded protein crowd against sensitive neurons. These plaques, composed. Ingram, elected to the. National Academy of Sciences in 2. His research is likely to have wider implications for other protein- based diseases, such as Huntington's. Working with misshapen proteins is not new for Ingram. Early in his career, he discovered that. His interest in science was apparent early on. He was always tinkering with things. Although radio receivers were. Nazi Germany, he constructed them from scratch; he took the risk so he could listen to what was going on outside. When he was 1. 4, his family moved to London to escape the environment of Nazi Germany. Although his degree program focused on chemistry, math, and zoology. Birkbeck offered weekend classes, an advantage, Ingram points out, in wartime London. Many of Birkbeck's students were, and still. During the day, Ingram worked at a chemical factory making drugs, like amphetamines, that. Ingram remembers a set of “better than the usual lecturers” brought to the city through their. Ministry of Defense. He fondly remembers Graham Jackson, who had such a talent for teaching that he “made the. Alistair Graham's lectures got him interested in animal physiology, which, according. Ingram, “naturally led to biochemistry.” After receiving his B. S. Photograph courtesy of Donna Coveney (Massachusetts Institute of Technology). Upon finishing his Ph. D. By 1. 95. 2, Ingram. England but was frustrated by conducting a job search 3,0. After sending out 3. Fruton laboratory spurred Ingram's. Vernon Columbarium Vernon & District Family History Society Surname Given Name(s) Birth Date Death Date. Herbert Gutfreund, fresh from Cambridge, England, encouraged Ingram to apply for a position at the Medical. Research Council's Unit for the Study of the Structure of Biological Molecules in the Cavendish Laboratory of Cambridge University. This time he was in the laboratory. Max Perutz, who had hired him as a protein biochemist. Perutz needed someone to produce a derivative of hemoglobin with. Ingram applied himself and finished the project quickly and was then free to pursue his own work. The Cambridge neighborhood. Frederick Sanger, who had recently sequenced insulin and demonstrated. Perutz suggested that Ingram build on Sanger's work and. Ingram's own interest in characterizing the large fragments of hemoglobin by comparing normal hemoglobin to sickle cell anemia. Using samples of sickle cell hemoglobin left behind by a former visiting scientist, Tony Allison, and samples. Ingram set about his project. Hemoglobin. is 1. Ingram decided to digest the protein into larger, but still manageable, peptides using. He first looked for the particular segments that might differ between normal and sickle cell hemoglobin. In doing. so, he developed the first two- dimensional protein analysis. In the first step, he ran the proteins out in neutral buffer. After that, he used partition paper chromatography to differentiate the peptides further. The implications of the work also negated some of the early models of overlapping triplets coding for amino acids (4). If triplet codes actually overlapped, a single base substitution, like that for sickle cell anemia, would affect more than. He eventually published a book detailing the multitude of abnormalities in human hemoglobin (8). In 1. 96. 1, after submitting a cohesive body of publications and directing others in research, Ingram received the high degree. D. Sc. He humbly jokes about the degree, “The only benefit is that it entitles you to wear a particularly. Before long, he was back in the United States, this time for a longer visit. Medical Research Council. At the time, it was the norm for British scientists to spend a year or two in the U. S. He was offered a visiting associate professorship at MIT. He collaborated with. Paul Marks working on hemoglobin and spent a few days each month in Marks's laboratory at Columbia University (New York). By the late part of the decade, he had settled on. Alzheimer's disease. The shift was partially inspired from a conversation with his second wife. Beth. She was working as a physician's assistant with the mentally retarded in Boston, including those with Down's syndrome. Ingram hypothesized, “Sickle cell anemia is an inherited mutation. Maybe. in Down's syndrome, there is an inherited mutation in different neurofilament proteins.” It turned out not to be the case. Alzheimer's disease and Down's syndrome, Ingram confesses, “I was hooked.”. I am happy to have found candidate compounds for a simply awful disease.”All Down's syndrome patients develop Alzheimer's disease by the time they reach 4. In Alzheimer's disease, proteins normally produced by the brain. One of these peptides, . Thank you for taking the time to visit our website, which provides practical information and valuable advice. Whether you need to make funeral arrangements.The result, Ingram explains, can be physiologically. It very quickly aggregates, and some aggregates—not all—have toxic effects on nerve cells.”. What causes the onset of misregulation of peptide cleavage is unclear. And the exact causes of the pathogenesis are not agreed. Ingram believes that the aggregated protein presents a novel surface that interacts with. His research has suggested that the interaction causes pores to open, resulting in an influx of calcium. The rapid, uncontrolled influx of this potent signaling molecule hampers the neuron's ability to respond to other stimuli. He points to work done across the Charles River by Ashley Bush at Massachusetts. General Hospital (MGH) in Boston that focuses on the creation of toxic reactive oxygen species from the interaction of misfolded. Referring to Bush's work, Ingram notes, “I'm not saying that it is not so, but I think it is. The first thing that happens is a calcium influx. Reactive oxygen species have a role to play in pathology. I don't think they're the first cause.”. Regardless of the nature of the damage, Ingram says, “Most people agree that these fibrils are a toxic agent by some method.”. His laboratory is pursuing dual strategies to stop the damage and abrogate a disease that, Ingram notes, is beginning to affect. The second, detailed in Ingram's Inaugural Article (1. PNAS, seeks to obliterate the misfolded proteins. Using a high- throughput screen, Ingram and his colleagues. They found that the compound 4,5- dianilin- ophthalimide (DAPH) actually. Alzheimer's disease, and, by doing so, DAPH reduces the influx of calcium. Paul) are applying for funding to begin testing the compounds and decoy proteins in vivo. For 1. 6 years, he and Beth were housemasters in a graduate dorm at MIT. Some students became colleagues,” he says. Why does it work?”. This enthusiasm for science is complemented by his interest in art. An admirer of Georgia O'Keefe, Ingram is a passionate. But he does not have as much time to devote to art as he would like. Running. a research program takes most of his time, and he still occupies a spot at the bench.
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