Krzysztof Palczewski | |
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Born | 1957 (age 66–67) |
Alma mater | University of Wrocław, Wrocław University of Technology |
Known for | Rhodopsin |
Awards | Humboldt Research Award Prize of the Foundation for Polish Science (2012) [1] ARVO Friedenwald award (2014) [2] Contents[3] |
Scientific career | |
Fields | Biochemistry |
Institutions | Case Western Reserve University; University of California, Irvine |
Doctoral advisor | Marian Kochman |
Website |
Krzysztof Palczewski (born 1957) is a Polish-American biochemist working at the University of California, Irvine.
He is a Member of the National Academy of Sciences and the National Academy of Medicine.
In 2012 he was awarded Prize of the Foundation for Polish Science, the most prestigious scientific award for Polish scientists, for characterizing crystal structures of native and activated G protein-coupled receptor, rhodopsin, involved in eyesight. [1]
His MS and PhD, are from the University of Wroclaw and Technical University of Wroclaw, respectively (Poland). His early posts were at the University of Florida and the Oregon Health Sciences University. Dr. Palczewski completed much of his pivotal research at the University of Washington. In 2005 he moved to become the Chair and John H. Hord professor of Pharmacology at Case Western Reserve University. In 2018 he joined University of California, Irvine, where he is a Distinguished Professor and is leading the Center for Translational Vision Research. [4]
Palczewski's research interest lie in mapping the Visual Transduction System. His work with determining the crystal structure of rhodopsin has given new insight into the function of G protein receptors. Furthermore, his work on visual cycle has led to revolutionary advances in understanding hereditary blindness, leading to implementation of novel pharmacological treatments that can slow retinal degeneration in adults. [5] [6] His team's efforts indicate that repetitive 2-photon imaging of the human eye can safely reveal the visual system's sub-cellular architecture and that humans can detect infrared light due to simultaneous 2-photon absorption. [7] [8] Recently, Palczewski and co-workers applied a new generation of CRISPR technology, base editing as a treatment for inherited retinal diseases. [9]
Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction in rods. Rhodopsin mediates dim light vision and thus is extremely sensitive to light. When rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, after which the rods are more sensitive. Defects in the rhodopsin gene cause eye diseases such as retinitis pigmentosa and congenital stationary night blindness.
Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.
A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.
Rod cells are photoreceptor cells in the retina of the eye that can function in lower light better than the other type of visual photoreceptor, cone cells. Rods are usually found concentrated at the outer edges of the retina and are used in peripheral vision. On average, there are approximately 92 million rod cells in the human retina. Rod cells are more sensitive than cone cells and are almost entirely responsible for night vision. However, rods have little role in color vision, which is the main reason why colors are much less apparent in dim light.
Retinal is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).
Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.
Animal opsins are G-protein-coupled receptors and a group of proteins made light-sensitive via a chromophore, typically retinal. When bound to retinal, opsins become retinylidene proteins, but are usually still called opsins regardless. Most prominently, they are found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in vision. Humans have in total nine opsins. Beside vision and light perception, opsins may also sense temperature, sound, or chemicals.
Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.
Congenital stationary night blindness (CSNB) is a rare non-progressive retinal disorder. People with CSNB often have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients may also have reduced visual acuity, myopia, nystagmus, and strabismus. CSNB has two forms -- complete, also known as type-1 (CSNB1), and incomplete, also known as type-2 (CSNB2), which are distinguished by the involvement of different retinal pathways. In CSNB1, downstream neurons called bipolar cells are unable to detect neurotransmission from photoreceptor cells. CSNB1 can be caused by mutations in various genes involved in neurotransmitter detection, including NYX. In CSNB2, the photoreceptors themselves have impaired neurotransmission function; this is caused primarily by mutations in the gene CACNA1F, which encodes a voltage-gated calcium channel important for neurotransmitter release. CSNB has been identified in horses and dogs as the result of mutations in TRPM1, GRM6, and LRIT3 .
Rhodopsin kinase is a serine/threonine-specific protein kinase involved in phototransduction. This enzyme catalyses the following chemical reaction:
The photoreceptor cell-specific nuclear receptor (PNR), also known as NR2E3, is a protein that in humans is encoded by the NR2E3 gene. PNR is a member of the nuclear receptor super family of intracellular transcription factors.
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa or congenital stationary night blindness.
Retinal degeneration is a retinopathy which consists in the deterioration of the retina caused by the progressive death of its cells. There are several reasons for retinal degeneration, including artery or vein occlusion, diabetic retinopathy, R.L.F./R.O.P., or disease. These may present in many different ways such as impaired vision, night blindness, retinal detachment, light sensitivity, tunnel vision, and loss of peripheral vision to total loss of vision. Of the retinal degenerative diseases retinitis pigmentosa (RP) is a very important example.
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
José-Alain Sahel is a French ophthalmologist and scientist. He is currently the chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, director of the UPMC Eye Center, and the Eye and Ear Foundation Chair of Ophthalmology. Dr. Sahel previously led the Vision Institute in Paris, a research center associated with one of the oldest eye hospitals of Europe - Quinze-Vingts National Eye Hospital in Paris, founded in 1260. He is a pioneer in the field of artificial retina and eye regenerative therapies. He is a member of the French Academy of Sciences.
Emixustat is a small molecule notable for its establishment of a new class of compounds known as visual cycle modulators (VCMs). Formulated as the hydrochloride salt, emixustat hydrochloride, it is the first synthetic medicinal compound shown to affect retinal disease processes when taken by mouth. Emixustat was invented by the British-American chemist, Ian L. Scott, and is currently in Phase 3 trials for dry, age-related macular degeneration (AMD).
Paul Hargrave is an American biochemist whose laboratory work established key features of the structure of rhodopsin.
Paul A. Sieving is a former director of the National Eye Institute, part of the U.S. National Institutes of Health. Prior to joining the NIH in 2001, he served on the faculty of the University of Michigan Medical School as the Paul R. Lichter Professor of Ophthalmic Genetics. He also was the founding director of the Center for Retinal and Macular Degeneration in the university's Department of Ophthalmology and Visual Sciences.
Denis Aristide Baylor was an American neurobiologist. He was professor emeritus of neurobiology at Stanford University. He is known for his research on nerve cells in the retina of the eye. He developed a widely-used method for observing the electrical activity of single rod and cone photoreceptor cells and described how they encode light stimuli. Baylor’s work has been recognized by his election to the American Academy of Arts and Sciences, the National Academy of Sciences, and the Royal Society of London.