The human eye consists of focusing elements and photoreceptors. Images are formed when light is projected onto the retina, which houses photoreceptors called rods and cones. These cells then relay the focused light into our optic nerves
and, subsequently, brains. Typically, cones can only perform optimally with relatively large amounts of light while rods are much more sensitive and perform well in lower light. The strongest images are presented by focusing the light onto the fovea centralis, where the highest concentration of cones is found. Interestingly, the fovea can present a ‘blindspot’ in dim light as rods that account for more peripheral vision can detect low light where cones cannot. Dark adaptation of vision occurs most optimally after 30 minutes.
Science for the Masses, a group based in Tehachapi, CA, may have just found a way to grant humans night vision without goggles. Their work is based heavily on a chlorophyll analog called chlorin e6 (Ce6) a protein typically used as an anticancer drug, an antibacterial, and nanoformulation.
Ce6 has a high molar absorption in the spectral red region and can be easily produced using Chlorella or green plants. For these reasons, it has garnered much attention as a photosensitizer. In human medical treatment as an anticancer drug, Ce6 is used for its ability to amplify light from low power light sources. This allows a medical team to target cancer cells with precision. The reaction that Ce6 undergoes produces harmful oxygen species that kill the tumor cells. It has also been demonstrated to be effective as an antibacterial.
This ability to increase photosensitivity has promoted notions of creating a treatment for nightblindness. Taking notes from a patent that discusses this very idea, Jeffrey Tibbetts and Gabriel Licina have been able to show increased vision in low light situations when administered to an individual with healthy eyesight.
Using the mixture of Ce6, saline and insulin found in the patent, Licina was dosed 3 times with 50uL in each eye. Sunglasses and dark sclera lenses were used after dosing to ensure low light conditions and reduce the potential for damage due to light exposure. Licina made up the only test subject; 4 other individuals constituted the control group.
At 10 meters, Licina could identify different both static symbols and moving symbols against different backgrounds, At 50 meters, Licina could detect individuals standing among trees in the woods with 100% accuracy, as compared to a control group not dosed with Ce6 who had about 30% accuracy. The effects seem to wear off by the next day.
While this treatment certainly seems to open doors, it should be noted that much more extensive research is required. While no damage has been noted by the authors, a much larger sample size is required for safely administering this drug. Exact measurements to test the true extent of enhancement would also help in evaluating this treatment’s efficacy. On a cellular level, how does this chemical affect our rod and cone populations? Could it extend our sight farther down into the red? At what level of darkness does detail begin to fade?
The future is almost here!
My research is broadly focused in circadian rhythm, and as a second year graduate student, I am still expanding my knowledge in this field. The more I read, the more I realize that everything is connected! Circadian rhythm can be described at many levels. There are transcriptional cycles, translational cycle, post-translational modification cycles, and even metabolic cycles. As it turns out, all to of these circadian rhythms are not coincidental, but rather, they are mostly a result of environmentally regulated mechanism such as light, nutrition, and hormonal stimuli. For the average animal, cycles of daylight, eating, and hormone release are set to the pace of their environment, and evolution has been selective for organisms that can anticipate their environments. Thus, circadian rhythms are highly conserved across the animal kingdoms. Although circadian regulation occurs at each level of gene expression, it all begins with transcription. The transcriptional circadian cycle can be attributed to transcription factors (CLOCK and CYCLE/BMAL) which bind to E-box elements and promote downstream gene expression. Of these genes, two of them (PERIOD and TIMELESS/CRYPTOCHROME) return to the nucleus to inhibit CLOCK and CYCLE activity and their own transcription. This negative feedback loop takes approximately 24h and defines the circadian period. One of the most important regulatory mechanism underlying this cycle is that of post-translational modifications (PTM) which establish the timing of PERIOD and TIMELESS inhibitory activity.
PTM regulation has been well defined in terms of phosphorylation, but the field of PTM regulatory mechanisms has barely scratched the surface. There are numerous ways a protein can be modified and even more ways in which this can affect protein activities. The articles I have selected provide an example for the importance of PTM in the circadian cycles of the liver. Metabolic health is a growing concern worldwide due to the number of people who suffer from metabolic diseases or malnutrition. The first article http://www.sciencedirect.com/science/article/pii/S0092867413014852 is a study from 2013 that illustrates the dramatic shift in transcriptional and metabolic outputs in response to nutritional challenges. It is compelling to consider what implications this has for people who regularly face “nutritional challenges” such as high fat diets. The second article http://journal.frontiersin.org/Journal/10.3389/fendo.2014.00221/full is a review that discusses how high sugar and other nutritional challenges can affect enzyme activity in the liver by disrupting the PTM profile of those enzymes. Together, these articles support the notion that healthy eating is an important component of healthy protein function. There are a number of other ways that good nutrition supports healthy cells, metabolism, and hormone balance, but when it comes to my area of focus, I see it all through the lens of protein regulation by PTM. Perhaps a full profile of PTM in healthy and unhealthy people could establish new guidelines for future healthcare as a point of diagnostics and therapeutics. Then again, it might be easier to just eat a salad every now and then.
Cheers to good food and good PTM!
BMCDB Graduate Group, UC Davis
“We first used baker’s yeast, which is an established aging model, and noticed that the yeast treated with ibuprofen lived longer,” said Dr. Michael Polymenis, an AgriLife Research biochemist in College Station. “Then we tried the same process with worms and flies and saw the same extended lifespan. Plus, these organisms not only lived longer, but also appeared healthy.”
He said the treatment, given at doses comparable to the recommended human dose, added about 15 percent more to the species lives. In humans, that would be equivalent to another dozen or so years of healthy living.
Polymenis said the three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan, an amino acid found in every cell of every organism. Tryptophan is essential for humans, who get it from protein sources in the diet.
“We are not sure why this works, but it’s worth exploring further. This study was a proof of principle to show that common, relatively safe drugs in humans can extend the lifespan of very diverse organisms. Therefore, it should be possible to find others like ibuprofen with even better ability to extend lifespan, with the aim of adding healthy years of life in people.”
Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import
The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.
Many times in life, roads lead to the unknown – however much we may think we know the destination. This can be especially true for careers in science. Reading Ranjan Mukherjee’s story in Science Careers is an inspiration to keep an open mind.
Briefly summarized, he graduated with a Masters in physics from the University of Calcutta and was accepted into a biophysics PhD program at the University of Delaware. Leaving behind family and friends in India for his unknown (otherwise called Newark, Delaware), he found his adviser-to-be had passed away some months ago and no one had notified him. Suddenly met with much more unknown than one could hope for, he adapted. While teaching physics labs to fulfill student visa requirements and heterotrophic obligations, he convinced a faculty member in biology to take him on.
After earning the PhD and getting married, a postdoctoral position in Strasbourg, France meant meeting another unknown. This led to a drug discovery position targeting metabolic disease, a field in which he would spend the next 22 years. However, after 15 years at a particular company, his position in R&D was unexpectedly eliminated.
Drawing on a love of travel and writing, he sent off fresh articles to blogs and journals. A few have been picked up by a magazine, a major newspaper, and the Indian government to advertise for tourism. He is now embarking further into the unknown, launching a new writing career. It is no wonder the title of this article is “The Winding Road.”
While career trajectory often hangs heavily above anyone starting out in science, it is important to remember that life can take us anywhere and we shouldn’t always take little discouraging things (like suddenly finding out that your adviser-to-be is no more after moving halfway across the world) as discouragement. A sharp bend in the road may not necessarily mean going off the cliff, and a winding road can take you to new, incredible places.
S.M. Theg Lab
See the article at:
Science 21 November 2014: Vol. 346 no. 6212 p. 1026 DOI: 10.1126/science.346.6212.1026 PMID: 25414316
Just FYI. There will also be an ice cream social in the courtyard after the meeting.
Great fun and food for all!
Thanks to the Night Lab at UCol. Boulder for putting this together.
“The assembly of an infant gut microbiome framed against healthy human adults ”
“Here we present how a new born human gut microbial community develops from resembling the delivery method (vaginal) to look like, after almost 3 years of life, the one of an adult. This trajectory is created from the data published by Koenig JE et al. 2011 framed around the data generated by the Human Microbiome Project (HMP).”