Meditations of an oncology geek

Archive for June, 2012

Why do all our cells contain the same DNA?

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25 June 2012

Yesterday I had lunch with my grandpa at a very nice outdoor Cafe down in La Jolla. He reflects a keen intellect and curious disposition sharpened by more than eight decades of life experience. A social man, he has garnered many friends of similar curiosity in his community. Whenever we meet up for lunch it is early impossible not to run into people he is familiar with, and I often have the pleasure of meeting more experienced curious minds.

Shortly after introducing me to yet another one of his friends, I had the pleasure of having an impromptu conversation on the revelations (and subsequent mysteries presented) by a certain major find of the late 20th century: more or less, all of the cells in our bodies have the same genomic DNA. What Milt wanted to know, was why?

Fundamental questions are often framed under: Who What When Where Why and How? When it comes to the natural world (of which we are a part) it is the Why that is perhaps the most perplexing.

Almost all of the cells in our bodies have the same sequence of genomic DNA. There are some exceptions, of course: our cells also have a certain amount of DNA housed in mitochondria, and some cells, like red blood cells, contain no nuclei and no genomic DNA. Although we all contain DNA sequences that differ slightly from person to person, within an individual almost all of the trillions of cells in the body have the same DNA sequence. With all the different cell types that exist, how can this be?

One answer to that question is epigenetics. Literally, epi- (above) genes. Imagine a book that contains 300 pages. We’ll title this book “Genomic DNA.” In the basal skin cell edition, pages 50-67, 103-245 and 278-290 are all glued together and cannot be read. In the muscle cell edition, pages 23-60, 98-110, and 115-250 that are glued together and cannot be read. The list goes on. Although all of the books for the various cell types technically contain the same code, not all of the code can be read. This is true for genomic DNA: processes like methylation and acetylation allow preferential reading of certain sections of the code. It is the pattern of these processes that varies between cell types.

But, this does not quite answer the “Why?”

Milt asked, if there are parts of the genome that are not useful for, say, a skin cell, why keep it around? Surely it must have taken a lot of energy and cellular resources to write all those pages that cannot be read, and the extra space in a cell it takes up could be used for something else?

While it might be impossible to come up with an unequivocal answer for that one, I would like to remind my dear readers that there are no absolutes in science: there are only greater levels of certainty. There is rarely any true black or true white, but many, many shades of gray in the emerging picture of biological systems, and this picture is subject to change as we gain more data about the world.

What I can offer is the best possible explanation given what we know about biological systems. And that answer is fairly simple: natural selection demands adequacy, not perfection.

Above is an image of a man-made circuit. Below is an image of an evolution-made circuit. Natural selection rarely produces something de novo. Usually, it takes something that already existed (like a particular protein) and tweaks it in slight ways that allow it to fill additional or unique roles. It would be like building a house one room at a time without a master plan. As such, biological circuits tend to be very disorganized and contain a high amount of redundancy: they make that multiple outlet adapter with the cords to your computer, screen, printer, fax, etc look orderly and neat by comparison.

At risk of sounding circular, you and I tend to think like humans. Humans like to organize thoughts into categories and streamline processes. The best humans esteem perfection. Natural selection does not produce perfection, it produces survival. Natural selection’s attitude is: if the shoe fits, wear it. Don’t fix something that’s not broken.

Looking deeper into other cellular processes, one begins to find many examples of energetically expensive or redundant cellular pathways. Perhaps there is a reason to keep all those glued together pages in that book? Maybe it would take too much effort and energy to remove them? Maybe removing them would risk damaging adjacent pages that need to be read correctly to make a skin cell and not a skin cancer?

Again, there is no absolute answer to the question of WHY all of our cells contain the same DNA if not all of it is used. But, I hope that this blog entry helps to explain some of the nuances and depth to this mystery.

-Ryon

Written by Ryon

June 25th, 2012 at 10:58 am

Posted in Science Blog

How the Race Across America was won: Congrats Team ViaSat

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23 June 2012

Dear readers,

This entry is a break from my blog’s typical subject matter. As a scientific apprentice, most of my time is devoted to my research. Outside of lab, I’ve had the opportunity to put my science hat on for a slightly different project: assisting Team ViaSat in their quest to win the grueling Race Across America.

The Race Across America (RAAM) is exactly as it sounds: It’s a bike race from Oceanside, CA to Anapolis, MD. In many ways it harkens back to the early Tour de France: without professional teams, regular working men were up against the unknowns of human endurance and mental fortitude. The modern Tour de France has well-defined time and television schedules, with races lasting 5-7 hours each day. RAAM has only one stage, and racing goes through the nights, 24 hours a day. It is a tremendous undertaking for both athletes and supporting crew during the race, and requires extreme preparation and attention to detail that must be logged long before reaching the start line.

Photo: The race goes through Monument Valley in Utah. Source: Pink Shorts Photography.

Teams from around the world come to compete in the 8-man RAAM, they vary widely in their resources, preparation, and strategy. Some teams are attracted to the race to venture into the unknown, or as an excuse to see the country with a bunch of their friends. Other teams are modeled after Formula One squads, with highly refined roles, ex-olympians, big sponsors, and extreme attention to every detail. Enter Team ViaSat: A group of working men that have two things in common: they love riding their bikes fast and are obsessed with winning RAAM. Who were they to compete with the better funded Team Type One, Strategic Lions (UK), or 4Mil?

In the spring of 2010 Swamis had a very good Thursday morning team time trial workout at Fiesta Island. I would ride my time trial bike down early in the morning for the pre-work workout, and one of the few people I’d see on the road coming (really fast) the other direction was this dude carrying a messenger bag whose over-the-top body language reflected the upbeat music in his earbuds.

The Swamis workout always met at the causeway before the more structured workout, and one morning that guy in the ViaSat cycling kit came up and introduced himself. The man was none other than Andrew Danly, who is known to many by his very appropriate nickname: METAL. Immediately after introducing himself I was absolutely shocked to have him ask if I wanted to do the Race Across America (RAAM) as part of his 8-man team. It was one of those out-of-left field moments that don’t come around so often and was surely one of those life-changing opportunities. But, after considerable thought I determined that I had too much on my plate already as a young graduate student, and respectfully declined.

Photo: They let me lose with a marker and whiteboard. Here I am making recommendations for pacing based on fat oxidation curves matched with terrain percent grade.

In 2010 the hodgepodge ViaSat team of close friends and dedicated crew went on to get 2nd place, behind the much better funded Team Type One, a team primarily dedicated to professional cyclist development. The following year, the dedicated crew of ViaSat took their trip to the batter’s box, and delivered a very good race while their “A” riders cheered on.

For 2012, it was all in for the veterans on the ViaSat squad. Crew and riders were equally focused on the task at hand. In that time my requirements got even more demanding for my PhD, and when I was approached again about being part of this all-star squad I flirted with it for a few months, before again respectfully declining. I simply did not have the time to do the demanding endurance training for the race. The ViaSat squad are all working men and women, and they completely understood my obligations as a young professional.

One of the really cool things about the ViaSat squad is that most of their riders and crew are located in San Diego, and with cycling being a highly social sport as it is, I quickly became friends with the riders. Even though I could not race RAAM I was nonetheless fascinated by the unique equipment and biochemical demands of the race.

I started joining in on their Saturday morning workouts, and endless discussions on the topics of gear, physiology, psychology, and metabolic biochemistry eventually evolved into more formal team meetings on the topics (see photo). While the riders were already experienced in the aforementioned topics, I saw the opportunity to act as a scientifically literate objective outside observer to help them refine their approach. Monthly meetings and time trials followed by extensive photo and data analysis were a big part of the process. Weaknesses were mitigated and changes in gear and approach were applied in anticipation of the unique demands of RAAM.

The result?

Team ViaSat went on to win the race with a NEW COURSE RECORD of 5 days, 5 hours, and 5 minutes. Over the Rockies and Appalachia and everything in between from Oceanside, California to Annapolis, Maryland their average speed was a staggering 23.94mph! They went so much faster and were so much farther up the road that veteran crew got to traverse (and see) areas of the country obscured by night time darkness in previous editions of the race.

For Team ViaSat, this was a momentous achievement four years in the making. It was the result of countless hours of athletic training, logistical preparation, and strategic planning mixed with blood, sweat, tears, and raw passion for the sport and the race. Words, photographs, and video can not adequately describe this very human effort.

I am honored to have been a part of such a unique and stellar achievement. I may never be part of a Formula One or an America’s Cup team, but for the rest of my life I can know that I was part of the team that won the Race Across America. Andrew “METAL” Danly offered these kind words:

“Ryon you are part of that win and the entire teams knows your role was instrumental in a way that only we racers will ever know. I’m certain, that record is yours too because you forced us all to get even faster. Cheers coach!”

A few hours after results were made official, back in California a toast was raised in their honor. By ironic contrast, what’s next for the highly organized ViaSat team is enigmatic, but I am certain that it will include riding bikes, a good steak, and fine San Diego beer.

Chapeau, Team ViaSat!

Ryon

Written by Ryon

June 23rd, 2012 at 8:10 am

Posted in Science Blog

Cell Death and a little science humor

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This is quite literally what goes on every day in all of us. We are made of trillions of cells, and these cells are constantly undergoing quality control and checkups. By some estimates, 50-70 billion cells undergo programmed cell death (Apoptosis) every day. It is very important to understand that we are all constantly dying and being re-made, and apoptosis is essential to maintaining healthy tissues. It is when this equilibrium is perturbed that cancers can arise, and when cancers can spread and metastasize.

Admittedly, I am a bit biased, as this area of cell biology is very near to my heart. (See Research)

Written by Ryon

June 19th, 2012 at 8:53 am

Posted in Science Blog