Basic Prion Science “Spreads” Insight
نویسنده
چکیده
Translational research used to be fun. In fact, it used to be arresting—of course, considered here in the frame of triplets and ribonucleic acids of the transfer and mRNA variety. In fact, the mind-boggling concept that someone could actually know the velocity of a ribosome trundling down a messenger RNA, like a freight car on a railway track, led me to decide at a tender age that biochemistry was the only way to go. On a journey that included a compressed but vigorous stint in Switzerland (“molecular biology boot camp”) and postdoctoral training with an eminent retrovirologist, my budding scientific life stood at a crossroads. What to do next? At this point, I had a reconnection with a moment from the past, in which a second-year, undergraduate version of myself read about an infectious agent called scrapie that didn't have a nucleic acid genome—bizarre! A serendipitous meeting, and this loose end was closed off; several productive research years were spent studying prions in San Francisco. Fast-forwarding through the nineties and noughties, we come to today’s world, where the N in GANTT doesn’t mean an ambiguous nucleotide but might mean that a progress report needs filing. For most basic biomedical scientists, the drone of the Translational Research mantra to leverage and commercialize can no longer be ignored; that ideology is enacted. The perception that taxpayers are being given value for money is the key driver in this equation, but how best to travel from a research lab environment to a Point A of a deep insight and thence, perhaps, to Point B of a significant impact upon delivered health care or a Point C of a commercialized platform technology? Perhaps the crux of the dilemma arises from a confusion of expectations and disciplines by politicians. Research and development (R&D) has predictability, a linear trajectory, and short timelines but may offer only shallow insights. R&D is certainly the logical option if one assumes that everything that can be discovered has already been discovered. On the other hand, basic research assumes that the catalog of ground rules for phenomena in the natural world is still being written; it has risk, as it lacks predictability and linearity. A benefit of basic research is that it routinely supplies a rigorous training environment. A yet bigger benefit— albeit less frequent—is that it provides “transformative” insights that can satisfy all expectations and deliverables. However, basic science can suffer from a variation on the theme of giving tax-payers value for money; namely, if the lay public or a Congressman (or, in Canada, a Member of Parliament) can’t understand the project, then they are not satisfied, period—the initiative is deemed wasteful/weird/esoteric and a negative message is directed to the controllers of the research agency. Prion research has had a profound and lasting impact upon Biology-with-a-capital-B and illustrates these principles with its own trajectory—a trajectory that probably would not have been funded in a purely translational world. The molecular biology of these diseases emerged from the study of an arcane sheep infection that was more agricultural nuisance than life
منابع مشابه
Mechanistic prospective for human PrPC conversion to PrPSc: Molecular dynamic insights
PrPC conversion to PrPSc isoform is the main known cause for prion diseases including Crutzfeldt-Jakob, Gerstmann-Sträussler-Sheinker syndrome and fatal familial insomnia in human. The precise mechanism underling this conversion is yet to be well understood. In the present work, using the coordinate file of PrPC (available on the Protein Data Bank) as a starting structure, separate molecular d...
متن کاملHigh prevalence of prion protein genotype associated with resistance to chronic wasting disease in one Alberta woodland caribou population
Chronic wasting disease (CWD) is a prion disease found in deer, elk and moose in North America and since recently, wild reindeer in Norway. Caribou are at-risk to encounter CWD in areas such as Alberta, Canada, where the disease spreads toward caribou habitats. CWD susceptibility is modulated by species-specific polymorphisms in the prion protein gene (Prnp). We sequenced Prnp of woodland carib...
متن کاملBasic Science Seminars in Neurology
C ompared with that of other human pathogens, the proposed replicative cycle of prions is disarmingly simple. It encompasses misfolding of a single protein, the cellular prion protein (PrP), into a disease-associated form called PrP. This is followed by PrP aggregation and possibly fragmentation of aggregates, which may augment the number of replicative units. Although there is no formal proof ...
متن کاملFrom Slow Viruses to Prions
I entered the prion field in the early 1990s, when the nature of the infectious agent was still in dispute. At one of the very first scientific meetings I attended, a spirited argument broke out between the proponents of a viral etiology and the proponents of the protein-only (prion) etiology. One of the strong arguments made that day against the protein-only hypothesis was the observation that...
متن کاملLRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein.
The trafficking of normal cellular prion protein (PrPC) is believed to control its conversion to the altered conformation (designated PrPSc) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrPC on neurons is rapidly and constitutively endocytosed by means of coated pits, a property dependent upon basic amino acids at its N-terminu...
متن کامل