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