Have you ever had a day where you feel exceptionally good? As in take on the world kind of good? You feel so much better than the previous couple of days that you stop to wonder why.
Then it dawns on you.
The sun is out. It’s been cloudy for the past week but now—SUNSHINE.
You go out to lunch or for a walk just to take in those rays. Sure, it feels warmer than your darkened office space, but it’s the light rather than warmth that’s making a difference.
You purposely don’t wear sunglasses and it feels like the light is coming in through your eyes and massaging that part of your brain that is your happy zone. Are you imagining it or is the sun really affecting how you feel?
In a study reported in the September 2018 issue of Cell we learn that this is not a figment of your or my imagination (1). There is, in fact, a type of retinal cell that transports sunlight directly to the part of our brains that affects mood.
Eyes and the Body’s Master Clock
Circadian rhythms are innate time-keeping functions found in all multicellular organisms. This subject of the 2017 Nobel prize in Physiology or Medicine, circadian rhythms are fueled by daily light-dark cycles and are critical to the function of neurologic, immune, musculoskeletal and cardiac tissues (2). Nearly every mammalian cell is affected by circadian rhythms.
The human body has a circadian master clock, the suprachiasmatic nucleus or SCN. The SCN is a highly innervated tissue located in the hypothalamus (see image). It is connected directly to the retina by the optic nerve, and thus is influenced by external light and dark.
The retina of the eye is the light gathering instrument for this organ. Historically, it’s been understood that the retina is composed of two cell types, rods and cones, that function in transmitting light and images to the optic nerve, which sends those signals to the brain.
Studies by Hattar et al. in the early 2000s identified that another cell found in the retina, the melanopsin-containing intrinsically photoactive retinal ganglion cells (ipRGCs) as the transmitter of circadian light signals (3). Through this direct connection to the SCN, the circadian master clock, the ipRGCs can influence a wide range of light-dependent functions independent of image processing (4).
Now Fernandez et al. have identified multiple types of ipRGCs. They showed that ipRGCs that mediate the effects of light on learning work via the SCN, while the pathway for light influencing emotions is different.
They discovered a new target of ipRGC cells, the perihabenular nucleus (PHb). The PHb is a newly recognized thalamic region of the brain. The authors showed that the connection between light and mood is regulated by ipRGCs through the PHb versus the SCN. They show that the PHb is integrated into other mood-regulating centers of the thalamic region.
Daylight, and lack thereof, does affect both our mood and our ability to learn. In this 2018 report, we have learned that the pathways for these effects are distinct, and gain an understanding of a new thalamic region by which the light and mood actions occur. This information could influence development of better drugs and/or therapies for major depressive disorders.
For those of us with seasonal affective disorder, the evidence is undeniable—lack of light can cause issues, from sleep-wake problems, to mood and learning issues.
And while we can’t create sunshine, a special lamp or light box may help to gain some full spectrum light. To learn more about how to choose such a lamp and when to use it, see this Mayo clinic article for details.
Glycobiology is the study of glycans, the carbohydrate molecules that cover the surface of most human cells. Glycans attach to cell surface proteins and lipids, in a process called glycosylation. These cell surface structures are responsible for processes as varied at protein folding, cell signaling and cell-cell recognition, including sperm-egg recognition and immune cell interactions. Glycans play important roles in the red blood cell antigens that distinguish blood types O, A and B.
Opportunities in Glycomics Research
As more is learned about the role of glycans in cell communication, they are becoming important disease research targets, particularly the role of glycans in cancer and inflammatory diseases (2).
Kinase target engagement is a new way to study kinase inhibitors for target selectivity, potency and residency. The NanoBRET™ TE Intracellular Kinase Assays enable you to quantitate kinase-inhibitor binding in live cells, making these assays an exciting new tool for kinase drug discovery research.
Late in 2017, a group here at Promega launched an exciting new assay, the NanoBRET™ Target Engagement (TE) Intracellular Kinase Assay.
It’s easy for me to call this assay exciting; I was an editor on the project team. But judging by the reviews on the SelectScience® web site, others are excited about NanoBRET™ Target Engagement Intracellular Kinase Assay too.
BTK (Bruton Tyrosine Kinase): Importance in Health and Disease
Bruton’s tyrosine kinase (BTK) was initially identified as a mediator of B-cell receptor signaling in the development and functioning of adaptive immunity. More recent and growing evidence supports an additional role for BTK in mononuclear cells of the innate immune system, especially dendritic cells and macrophages. For example, BTK functions in receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. BTK has recently been identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome (2). Continue reading “Kinase Drug R & D: Helping Your Inhibitor Make the Cut”
The review “Kinase Inhibitors: the road ahead” was recently published in Nature Reviews Drug Discovery. In it, authors Fleur Ferguson and Nathanael Gray provide an up-to-date look at the “biological processes and disease areas that kinase-targeting small molecules are being developed against”. They note the related challenges and the strategies and technologies being used to efficiently generate highly-optimized kinase inhibitors.
This review describes the state of the art for kinase inhibitor therapeutics. To understand why kinase inhibitors are so important in the development of cancer (and other) therapeutics research, let’s start with the role of kinases in cellular physiology.
Joins Nominees for Best New Drug Discovery & Development Product 2017
We were honored recently to have NanoBRET™ Target Engagement Intracellular Kinase Assays nominated by SelectScience® as one of the Best New Drug Discovery & Development Products of 2017. This is a Scientists’ Choice Award®, an opportunity for scientists like you worldwide to vote for your favorite new drug discovery/development product.
We are super excited about both the nomination and the NanoBRET™ Target Engagement Intracellular Kinase Assay. Here is a little information about the assay.
The Foundation for Food and Agriculture Research (FFAR) announced on November 30 that they are awarding $1M to a project based at the University of California, Davis, to study protein kinases of rice plants. The team is led by Dr. Pamela Ronald, a leading expert in plant genetics who has engineered disease- and flood-resistant rice. This project aims to address the growing agricultural problem of water scarcity by gaining a better understanding of the role kinases play in enabling drought-resistance. Promega will be supporting this research by providing NanoBRET™ products to help characterize kinase inhibitors.
The research team will begin by screening over 1,000 human kinase inhibitors to determine which ones do interact with the plant kinome and, if applicable, which kinase(s) they inhibit. Once the compound library has been established, the team will assess the inhibitors’ phenotypic effects on rice to identify kinases that, when inhibited, positively impact root growth and development. The long-term goal is to use these findings to engineer drought-resistant rice.
“Glycobiology is the study of carbohydrates and their role in biology. Glycans, defined as ‘compounds consisting of a large number of monosaccharides linked glycosidically’ are present in all living cells; They coat cell membranes and are integral components of cell walls. They play diverse roles, including critical functions in cell signaling, molecular recognition, immunity and inflammation. They are the cell-surface molecules that define the ABO blood groups and must be taken into consideration to ensure successful blood transfusions.
The process by which a sugar moiety is attached to a biological compound is referred to as glycosylation. Protein glycosylation is a form of post-translational modification, which is important for many biological processes and often serves as an analog switch that modulates protein activity. The class of enzymes responsible for transferring the sugar moiety onto proteins is called a glycosyltransferase (GT).”