A Dog’s Tale

By Sally Burn

2014 may be the Year of the Horse, but dogs have started the year as a scientist’s best friend, giving paws for thought in several recent papers. Freedman and colleagues barked up the right evolutionary trees to investigate canine evolutionary history, while Waller et al. report that puppy dog eyes give dogs a selective advantage when soliciting human care. Finally, a paper just published in Science sniffs out the genome secrets of an ancient transmissible dog cancer.

 

A Dog’s Tale Part I: The evolutionary history of dogs

Dogs and wolves share many traits but their exact evolutionary connection is unclear. A new paper out this month in PLoS Genetics attempts to address their phylogenetic relationship and reconstruct the early evolutionary history of man’s best friend. Adam Freedman and colleagues doggedly sequenced the genomes of three region-specific gray wolves, two basal dog breeds historically isolated from wolves, and a jackal outlier. Comparisons of these genomes (plus a boxer dog genome) revealed that modern wolves and dogs arose from a now-extinct common ancestor, contradicting the common notion that dogs simply descended from wolves that cozied up with humans. After the initial divergence, both the dog and wolf lineages went through severe population bottlenecks, resulting in increased disparity between their gene pools. The dog lineage was subsequently domesticated by hunter-gatherers, around 11-16 thousand years ago according to this new paper. Analysis was complicated by the fact that the genomes have not been in total isolation from one other, as extensive wolf-dog interbreeding has permitted further gene flow between the species. Such admixture and the extinction of the common ancestor have rendered the evolutionary history of dogs particularly hard to dissect, leading to vastly different conclusions from different research groups. Indeed, a study published last year concluded that population bottlenecks were not that significant during dog evolution. Another bone of contention has been the link between dietary adaptation and domestication. Grab yourself some kibble as we move on to that shaggy dog tale next…

 

A Dog’s Tale Part II: A dog’s dinner

The domestic dog is particularly fond of scraps from human tables. However, the human diet changed dramatically when we transitioned from hunter-gatherers to agriculturalists and so therefore did the digestive abilities of dogs. This was the conclusion of a study published in Nature in 2013, in which Erik Axelsson and colleagues discovered that dogs possess a number of gene variants associated with starch digestion. Compared to wolves, dogs have a seven-fold increase in copy number of AMY2B, a gene involved in the breakdown of starch. This was a necessary adaptation to share the starch-rich food of humans. The advent of agriculture was, they argued, a catalytic event in domestication as humans now had attractive scrapheaps, from which genetically-equipped wolves could steal tasty morsels. All of a sudden hanging with the humans was advantageous for survival and so the ancestor of modern dogs was born. In contrast, this month’s Freedman et al. study found that AMY2B copy number varies between dog breeds and is also high in some wolves, discrediting the notion of high AMY2B copy number being an explicitly dog trait. More specifically, AMY2B copy number is low in dog breeds not associated with agricultural societies, reaffirming their conclusion that domestication predated the onset of agriculture. The contrasting conclusions of the two papers demonstrate once again the difficulties in tracing canine evolution.

 

A Dog’s Tale Part III: Puppy dog eyes

Regardless of how they came to be able to digest our food, one thing we can be sure of is that dogs have a guaranteed mechanism for obtaining it: puppy dog eyes. Now researchers at the University of Portsmouth, UK, have found evidence that puppy dog eyes provide a selective advantage when soliciting human care. The team proposed that a key factor in dog domestication was human selection against aggression; they hypothesized that, in a process of co-evolution, dogs displaying pedomorphic (puppy-like) facial characteristics were preferentially selected by humans desiring increasingly tame canine companions. To test this hypothesis they used the speed of rehoming from shelters as a proxy for artificial selection. Humans stood in front of shelter pens and the facial expressions of the dog inmates were analyzed using a novel system called DogFACS (Dog Facial Action Coding System). As predicted, dogs who displayed puppy-like facial expressions were rehomed faster than those who did not. A key facial movement was the raising of the inner brow to make their eyes look bigger and more puppy-like. So next time you acquiesce and give doe-eyed Fido a superfluous treat, take solace in the fact that your weakness is just part of your DNA.

 

A Dog’s Tale Part IV: Transmissible dog cancer genome

Our final dog bulletin concerns the world’s oldest known cancer. Canine transmissible venereal tumor (CTVT) spreads when cancer cells pass between dogs during mating. Researchers at the Wellcome Trust Sanger Institute in Cambridge, UK, sequenced the cancer cells’ genome and published their findings last week in Science. They found that the cancer originated in a single dog around 11,000 years ago; the cancerous cells have been passed on ever since as a clonal lineage, long outliving the body from which they came and making CTVT the oldest known living cancer in the world. The cancerous cells still contain the genome of the dog in which the cancer arose, allowing the team to build up a genetic “identikit” of the first infected animal. The canine patient zero was a medium to large husky-like dog, with black or agouti fur. Mutation analysis pinpointed the origin to approximately 11,368 years ago. The cancer was initially contained within an isolated dog population but it became a worldwide problem around 500 years ago, possibly as a result of humans traveling the earth and taking four-legged companions with them. Some of these voyages may have been to sunny locales as the cancer’s genome bears hallmarks of exposure to ultraviolet light. The cancer cells have also undergone many other changes during their evolution, losing 646 genes and acquiring an estimated 1.9 million somatic substitution mutations – several hundred times the number found in most human cancers. Despite this accumulation of mutations the cancer cells have survived, illustrating just how robust mammalian somatic cell lines can be. Indeed, many of the mutations may have allowed the cancer to adapt to niche changes and thrive. While the cancer itself is rare, this study is of note as it chronicles the evolutionary history of a transmissible cancer. Further analysis of the cancer’s genome may therefore provide insights into the processes underlying cancer transmissibility.

Got Stripes? How the Zebrafish Got its Stripes.

 

By Sophia David

What do butterflies, snakes and fish all have in common? One answer could be that they all display colourful and spectacular skin pigmentation patterns. The zebrafish, for example, displays a beautiful and characteristic stripy pattern.

In the last decade, zebrafish, also known as Danio rerio, have emerged as an excellent model organism for studying vertebrate biology and, in particular, vertebrate development. This is due to the ease of maintaining large stocks of zebrafish, their quick development, and the transparent nature of zebrafish embryos and larvae. Luckily then, scientists wishing to study how pigment pattern formations develop already have a great model organism at their fingertips.

The zebrafish stripe pattern consists primarily of two types of pigment cell: melanophores (black pigment cells) and xanthophores (yellow pigment cells). Mutants that lack either of these types of cells do not show the stripy pattern.

Previous work by scientists from Osaka University in Japan previously showed that interactions between these two types of pigment cells are important for the development of the stripy pattern. In particular, they found that direct contact between xanthophores and melanophores causes the membrane potential of melanophore cells to change. This is called membrane depolarization. They hypothesized that the membrane depolarization of melanophores affects the movement of the cells and these movements, in turn, result in the formation of the characteristic pigment patterns.

In the study published this week in the journal PNAS, the same scientists tested and confirmed their hypothesis, and further characterized the interaction between the two types of pigment cell. They showed that the xanthophore cells reach out to touch melanophores by extending a part of their cell. These temporary projections of cells are called pseudopodia. Meanwhile, the melanophores show a repulsive response to the pseudopodia of xanthophores and move away. The xanthophores are not discouraged, however, and continue to chase the running melanophores. The authors called these “run-and-chase” movements. They believe that these movements cause the segregation of xanthophores and melanophores into distinct stripes.

The scientists further demonstrated that these run-and-chase movements are disrupted in mutant zebrafish that do not show the typical stripy patterns. For example, “jaguar” mutants have broader and fuzzier stripes. The scientists showed that the repulsive response of melanophores in jaguar zebrafish is inhibited compared to in wild-type zebrafish so essentially the melanophores cannot “run away” so quickly. This is thought to lead to the incomplete segregation of the two types of cell, resulting in broader and fuzzier stripes.

There is still much left to understand, however. The next steps are to understand the precise molecular mechanisms that occur when the two types of cells interact and how these lead to specific cell movements. Furthermore, the scientists want to understand how those mechanisms differ in the mutant zebrafish.

Can Black Soybeans Improve Blood Disorders?

 

By Lori Bystrom

Studies have suggested that eating a rainbow of colorful fruits and vegetables provides a diverse array of vitamins, as well as phytonutrients and other goodies for the body. So what benefits should we expect from black-colored foods?  In traditional Chinese medicine several “black foods” are believed to be a good source of nutrients and beneficial for blood production. A recent paper in the British Journal of Nutrition have evaluated several “black foods” and have found that black soybeans (Glycine max) affect a key regulator in iron metabolism and may be beneficial for certain types of blood disorders.

Hemoglobin is an iron-dependent oxygen transporter found in red blood cells. Low hemoglobin is indicative of anemia, as well as iron-poor and pale red blood cells. Anemia can result from dysregulation of iron metabolism or lack of dietary iron.

One of the master regulators for iron metabolism is hepcidin, a liver-derived peptide hormone that is encoded by the gene HAMP. Normally when excess iron is available, hepcidin levels increase and bind to the iron exporter ferroportin. This results in degradation of ferroportin and prevention of iron from being absorbed into the body, mobilized, and recycled for red blood cell production. However, some diseases, such as anemia of chronic disease (also known as anemia of inflammation) and iron-deficiency anemia, overexpress hepcidin regardless of the body’s iron requirements. Therefore, reducing hepcidin expression may have therapeutic implications.

Mu and colleagues tested extracts from several “black foods”, including black soybean, black fungus (Auricularia auricula-judae), black sesame seeds (Sesamum indicum), and date-plum (Diospyros lotus) for their effects on hepcidin expression in human liver cells. Only the black soybean seed coat extract (BSSCE) reduced hepcidin expression significantly. Interestingly, the iron content for this food was low and consisted of about 30% of anthocyanins, a pigment that most likely contributes to the blackish color of black soybeans. BSSCE also reduced the effects of a set of transcription factors (SMAD1/5/8) that activate HAMP gene expression. Moreover, induction of hepcidin gene expression by bone morphogenetic protein 6 (BMP6) and interleukin-6 induction (IL-6) was significantly reduced by BSSCE.

Animal studies also showed promising results. Mice were fed a diet consisting of 2% BSSCE for up to 30 days. At day 7, the mice had a 50% reduction in liver hepcidin expression and a 35% decrease in spleen iron concentrations, as well as a 135% increase in serum iron concentration. In other words, iron absorption and mobilization were increased in the mice. Moreover, by day 30 there was an increase in red blood cell counts (by 111%) and hemoglobin values (by 109%), as well as several other hematological parameters.

Similar to the vitro studies, there was a reduced effect on transcription factors (SMAD1/5/8) that activate hepcidin expression by day 7, but these effects returned to nearly control levels by day 30. In addition, the gene expression of 2 inducers of hepcidin expression (hepatic inhibitor of DNA binding 1 and BMP6), were also significantly reduced by day 7 and were slightly less affected by day 30. Other contributors of hepcidin expression were not affected. The researchers suggest that BSSCE may inhibit hepcidin expression by specifically inhibiting the signaling pathway that involves BMP/SMAD, but not the signal transducer and activator of transcription (STAT) pathway that also is associated with hepcidin expression.

This study suggests that BSSCE may be a potential dietary treatment for people with anemia of chronic disease or iron-deficiency anemia. Future studies will need to assess animal models with diseases that cause hepcidin overexpression to confirm the therapeutic benefits of BSSCE. Although it has not been confirmed, the authors suggest that the active component of BSSCE may be due to the anthocyanins in black soybeans. If these compounds and their effects are validated, then perhaps certain black pigments may shed more light on how blood can become a deeper shade of red.

 

 

 

 

The Art of Manipulation

 

By Sophia David

Parasitism is the most common way of life on Earth. It occurs when two species live in close proximity to one another and while one species (the “parasite”) benefits from the relationship, the other species (the “host”) suffers. Humans are only too familiar with parasites – the common flu virus, the tapeworm and the malaria parasite are just a few examples of organisms that parasitize our own species. While these organisms benefit from us by gaining shelter and food, we, of course, gain nothing but illness.

Through thousands of years of evolving together with their host (a process known as co-evolution), parasites have learned to manipulate their hosts in remarkable ways. The most unique example I have come across is that of a bacterium called Wolbachia. This is thought to be one of the world’s most common parasites. The hosts of Wolbachia are wide-ranging; they can infect numerous species of insects, spiders and worms. Sometimes, the relationship can be beneficial to the host, in which case the relationship is one of mutualism, where both species derive benefit, rather than parasitism. More often than not, however, the relationship is parasitism.

The defining feature of these bacteria is that they are transmitted to the offspring of an infected female host through the female’s eggs. Crucial to this story is that it is only female hosts that transmit Wolbachia, and not males. Instead, males are a dead-end host; once in a male host, the bacteria have nowhere to go. So, to enhance their transmission, Wolbachia would rather be in a female host than a male host. And they evolved the most fascinating mechanisms to achieve this. Like many parasites, they manipulate their host’s biology, but rather uniquely, they are able to alter their host’s reproduction in a way to favor their spread. In a paper by John Werren and colleagues from the US, the authors outline four fascinating ways in which Wolbachia can alter the reproduction of its hosts to its own advantage.

Cytoplasmic incompatibility

This sounds complicated but “cytoplasmic incompatibility” is just a way of saying that sperm from Wolbachia-infected male hosts is incompatible with eggs from females that do not harbour Wolbachia. This kind of match would produce offspring that are not infected with Wolbachia, since the bacteria can only be transmitted from the female. So Wolbachia has developed a way of manipulating the sperm of infected males so that they are only compatible with eggs that are also infected. It’s clever! The molecular mechanisms of how Wolbachia achieves this are still not properly understood though.

Parthenogenesis

Parthenogenesis is a type of asexual reproduction whereby embryos develop from eggs that have not been fertilized by sperm. While insects and other hosts of Wolbachia usually undergo sexual reproduction, parthenogenesis can also occur. Wolbachia makes use of this by ensuring only daughter progeny can be produced through parthenogenesis.

Male killing

Just as it sounds, Wolbachia are able to kill the male offspring of its hosts, usually when the embryos are developing. This gives the surviving, Wolbachia-infected females an advantage as more food and resources will be left for them.

Feminization

Even when Wolbachia is not able to kill the male embryos, it has another trick up its sleeve. By interfering with the sex-determining pathways of its host, it can cause genetic males to instead develop as females through a process known as feminization.

 

Different species and strains of Wolbachia use different combinations of these strategies to spread efficiently through host populations. Going to such extreme lengths, it is no surprise that they are among the most abundant parasites in the world.

Another characteristic of Wolbachia is that it inhibits the growth of many other microbes in its hosts. This feature, along with its remarkable ability to spread in host populations, has led to its use as a biological tool for preventing the spread of disease. One such disease is dengue fever, caused by dengue virus and transmitted by mosquitoes. The dengue virus is not able to survive inside a Wolbachia-infected mosquito. Therefore, scientists have created a strain of Wolbachia-infected mosquitoes which, when released into the environment, rapidly replace the non-infected population and prevent transmission of dengue fever. Small, pilot trials of this have worked well in Australia and larger trials are currently now taking place. In the coming years, Wolbachia could become a major, albeit slightly unusual, tool for combatting insect-borne diseases.

This post originally appeared on thetripletcode.wordpress.com

Backdoor Targeting of the Cancer Causing Protein K-Ras

 

Elaine To

When targeting a specific protein with a small molecule drug in order to treat a disease, scientists often use a molecule that mimics the natural substrate of the enzyme and targets the active site. However, this approach has met with limited success in the case of the oncogenic GTPase K-Ras. GTPases are regulatory proteins that act like binary switches for cellular pathways. In its “on” state, K-Ras is bound to GTP and activates signaling cascades responsible for cell growth, survival, and differentiation. When GTP gets hydrolyzed to GDP, K-Ras is turned “off.” Mutations that prolong the lifetime of GTP when bound to K-Ras, such as the G12C (glycine at position 12 is changed to cysteine) mutant, are highly oncogenic and lead to cancer. The high affinity of K-Ras for GTP and GDP makes drug targeting of the K-Ras active site difficult, but researchers Ostrem, Peters, et al. have discovered an alternate site on K-Ras that can be targeted for cancer therapies.

The researchers set out to find a small molecule that could specifically bind to the oncogenic G12C mutant protein while avoiding the wild type K-Ras by screening a disulfide library, which would be expected to react with the thiol group of the cysteine. Intact protein mass spectrometry revealed which compounds bound to the G12C mutant without targeting the wild type. The two strongest binders were unaffected by the presence of excess GDP, indicating that they do not compete with GDP for binding. X-ray crystallography showed that one of the strong binders was binding in a previously allosteric pocket of K-Ras.

In order to further characterize the novel allosteric site, the researchers examined libraries containing electrophiles, acrylamides, and vinyl sulphonamides for G12C K-Ras binding. Co-crystals of potent binders with K-Ras revealed that the switch-I and switch-II domains of the protein are disrupted, which also disturbs magnesium ion binding. Previously studied mutations in the residues that coordinate the magnesium ion result in a preference for GDP over GTP, thus the researchers tested the compounds for this activity as well. Indeed, exchange assays reveal a shift in K-Ras’s preference from GTP to GDP when the potent electrophiles are bound. Additionally, the compounds can block nucleotide exchange by exchange factors, though EDTA still effectively catalyzes the exchange of GDP for GTP.

It was also noted that the potent compounds occupied a position normally reserved for G60 when K-Ras is active. Known mutants of G60 have impaired binding to partner effector proteins such as Raf. Studies in cell lines show that compound binding impairs the association of K-Ras with Raf. Lastly, in order to show the effectiveness of the identified compounds as chemotherapeutic drugs, the researchers treat various cancer cell lines, some of which contain the G12C mutation. As expected, the cells with the mutation demonstrated significantly decreased viability in the presence of the compounds.

Overall, this is an elegant approach to small molecule drug development that fortuitously revealed a novel regulatory site of K-Ras. Drugs that target this site can be designed specifically for oncogenic mutations, and do not have to overcome the significant barrier of trying to out compete GDP and GTP for binding. The extensive crystal structure and enzymatic characterizations lay the groundwork for further drug development on K-Ras and may open up a whole new class of chemotherapeutic drugs.

Buzzkill

 

Tara Burke

The molecule pregnenolone protects the brain from marijuana intoxication

Ringing in 2014 brought the legalization of recreational marijuana (Cannabis sativa) sales in Colorado. As views towards the regulation of recreational marijuana usage continue to loosen in the United States and abroad, addiction to marijuana remains a serious problem. Cannabis consumers quest for a state of relaxation, however various dangers are associated with consuming cannabis including memory impairment, loss of motivation and withdrawal from social circles. Drug addiction clinics are seeing an increase in patients seeking treatment for marijuana addiction and consumption is particularly high in younger individuals ages 16 to 24. As a result of this increase, developing an effective treatment for cannabis addiction has become high priority in the field of drug addiction research. A recent publication in Science found a potential therapeutic target for treatment of cannabis addiction.

 

Scientists in Bordeaux, France administered various compounds of the major classes of abused drugs (cocaine, morphine, nicotine, alcohol and THC (the main active ingredient in marijuana)) and measured levels of pregnenolone in rats and mice. What they discovered was a 3000% increase in the amount of pregnenolone after administering THC. This increase was shown to happen through THC’s binding of the brain’s CB1 cannabinoid receptors and pregnenolone was show to be part of a feedback loop regulating the cannabinoid receptors. Therefore, THC binding to the cannabinoid receptors drove production of more pregnenolone, which in turn, blunted the response of the cannabinoid receptors and prevented them from producing a high. Until now, the naturally occurring steroid hormone, pregnenolone, was thought to be an inactive precursor to other steroid hormones such as estrogen and testosterone. In fact, because of this, it is currently sold over-the-counter as an anti-aging supplement.

 

This study also showed that pregnenolone administration blocked THC-induced food intake in rats and mice and stopped the memory impairment caused by THC in mice, two well-known behavioral disturbances of THC. More importantly, the administration of pregnenolone greatly reduced the release of dopamine triggered by THC. This is a vital finding if pregnenolone is to be considered as a treatment for marijuana addiction since addictive drugs involve the excessive release of dopamine, a gatekeeper of the brain’s reward and pleasure centers. The researchers in charge of this study hope that a new addiction therapy will emerge from this research. In fact, their studies continue with efforts now being focused on creation of a well-absorbed derivative of pregnenolone because when taken orally, pregnenolone is quickly converted into estrogen and testosterone.

 

In addition to addiction therapy, this discovery also has the potential to be helpful in other medical avenues. Blocking the intoxicating effects of marijuana may be beneficial to those that take it as an anti-seizure medication or anti-psychotic medication since these actions require a separate active ingredient of marijuana, cannabidiol. However, it is important to note that pregnenolone will not be useful to cancer patients and others using medical marijuana to alleviate pain or increase appetite since pregnenolone would block these effects of THC.  It will be interesting to see how development of pregnenolone progresses. With many potential uses and an increasing addicted population, I am sure drug companies are following this study closely as well!

5 Do's and Don'ts for Choosing Your Thesis Committee

 

Robert Thorn

As a 2nd year PhD student I know that picking a thesis committee can seem like an overwhelming decision. Having just gone through the process of picking a committee and setting up a committee meeting I’ve compiled some of the tips that I received to help you put together the best possible committee.

Do’s

1)    Pick PIs who have complimentary experiences to your own PI

Throughout your PhD training you will most likely be writing grants as well as papers. If your PI does not have much experience with graduate student training it may be difficult for them to help you in this writing. It is a good idea to have a committee member who can help you write and even co-sponsor you for grants if needed. This will help make sure your training is as successful as possible

2)    Pick a committee with diverse interests

This one goes along with #1. Just like you want a committee with different experiences from your PI, you also want committee members who have a range interests. By having this diversity you will be able to maximize the range of input you receive on project.

3)    Pick PIs you feel comfortable talking to

Remember that you will be stuck with this committee for most of your PhD career and they will be the ones who make the ultimate decision on whether you are qualified to graduate or not. By making sure you have a committee you can talk to, you can keep an open line of communication with your committee members and make sure you are reaching their expectations.

4)    Ask other students about PIs you are considering

If you know of other students who have had PIs on their committee they will be able to let you know. How are they with responding to emails? How open is their schedule? Are they open to talking outside of meetings? All these questions can be answered by your peers who have already gone through the process and help you make the final decision.

5)    Pick PIs who ask thoughtful questions

You want to make sure your committee helps guide you through the process of developing your PhD project. You can get a sense of the types of questions a PI asks by listening to the questions they ask during seminars and classes. Make sure that the questions the PI asks are going to fit with the way you want to receive feedback and so that their feedback can help further your project.

 

Don’ts

1)    Pick PIs who don’t get along

The last thing you want to worry about is whether or not your committee members will get along for a committee meeting. Asking your PI or other students about how different PIs get along with help keep drama out of your committee meetings.

2)    Pick too many busy PIs

It is very tempting to immediately pick a few high profile PIs to have a really high impact committee but this could backfire big time. Picking a time for a committee meeting can be difficult enough to begin with and the busier the PIs are, the more difficult it will be for you to get all your committee members together at one time.

3)    Pick PIs who talk too much about unrelated topics

Make sure the PIs you choose know how to keep their discussion to a limited amount of time. Even though committee meetings only happen once or twice a year, you still probably don’t want to have 3 or 4 hour long committee meetings because your committee members keep talking about tangential or unrelated topics.

4)    Pick selfish PIs

The point of the committee is to help you grow and develop your project. You definitely do not want a PI who will continually want to know how your project will relate back to their research. Make sure the PIs you choose will have your needs in mind during committee meetings.

5)    Make the decision lightly!

Your committee will play an integral role during your PhD, from guidance and advice to letters of recommendations for grants and post-doctoral positions you will rely on your committee for many different aspects of your training. Make sure to talk with your PI, lab mates and peers to get the best possible information you can while putting your committee together.

Have Do’s or Don’ts we didn’t mention? Share them with us!

9 Tips for Preparing for a Marathon When in the Lab

 

#JustDoIt!

Neeley Remmers

This year to celebrate the New Year, I spent New Year’s Eve on my couch studying for the MCAT and waiting until the clock struck 12:01 am so I could quickly get online to register for the Lincoln Marathon before it sold out (which it took less than 12 hours for it to sell all 12,500 spots). Fortunately, I got in and will be running my 3rd marathon this May (yippee!), so I thought what better way to kick off the race season and jump start my marathon prep than to compile a list of marathon do’s and don’ts for anyone looking to tackle the big one this year for the first time or for the 100th time.

1. Find a training program that works for YOU

There are numerous programs available for free online, and they all have three weekly key running workouts that are essential for you to be successful on race day: speed work, a mid-distance tempo run, and the long run.  I recommend following the FIRST training plan which only uses these key runs along with 2 days of cross-training. The thing I LOVE about this program is it is less time-consuming than other plans, which is a huge bonus since most of us spend a lot of time in the lab leaving little down time. Additionally, by cutting out the extra “junk miles” (normally termed “recovery run” in most programs) I found I was less likely to experience burn-out 4-6 weeks before race day.

2. Do your workouts in the morning

This will be a struggle for most since the typical lab day starts around 9:00-9:30 am and hitting the snooze button will seem like a much preferable idea compared to getting up at 5:30 in the morning to go run. But, we all know that lab experiments go awry and our days rarely go as planned. By disciplining yourself to get your run done in the morning, you can avoid making an excuse for yourself not to go run later in the day because it’s 7:00 pm and you’re JUST NOW leaving the lab.

3. Incorporate a strength training program into your marathon prep

Most assume that strength training will hinder their running ability because it will add bulk in which bulky muscles can make endurance running difficult. However, the right kind of strengthening can help prevent injury and actually improve your running performance. For strengthening, you can do anything from high intensity boot camp style classes to yoga to pilates; the key is to find a program that you find challenging yet enjoyable so you don’t dread these sessions. The more you dread a workout the less likely you are to actually do the workout.

4. Work on flexibility, especially in the hips and legs

Most runners tend to ignore the benefits flexibility can bring to their running performance. First, by keeping the hips loose, you can prevent any number of injuries including IT band flare ups, runner’s knee, and general pain in the knees and ankles. By simply adding 10-15 minutes of stretching at the end of any workout will keep your muscles from getting tight and thus, restricting your range of motion causing unnecessary strain in your joints and muscles.

5. Don’t do it alone

The first time you go on a long run that in your mind seems an impossible distance –  find someone to run it with you, ride their bike alongside you, or join you for the last few miles. This distance will be different for everyone, for me it was my first 16 mi run. Fortunately, the week I was slated to go on my first 16 mile run, I had just met a gentleman at the conference I was attending who was an experienced marathoner and offered to run with me. This helped tremendously because he served as my pace setter and provided encouragement towards the end of the run when I started to doubt if I could make it. But he kept me going and an added bonus was I immediately had someone with which to celebrate this huge milestone!

6. Tell your lab mates and mentor that you are training for a marathon

You will be amazed at how supportive they will be and this support system will be huge in keeping you motivated throughout your training and during your race.

7. Get fitted for the proper running shoes

Finding the right running shoes will give you optimal support to prevent pain in your knees and feet. If you want to try barefoot running or running in minimal shoes, do so with caution. Gradually build the distance you run in those shoes to give your body time to adjust.

8. Invest in running clothes

Especially in the clothes to wear during your long runs and on race day. Wearing any old cotton t-shirt will trap the excess heat your body will produce and become insanely heavy from all your sweat making you incredibly uncomfortable. Running clothes are designed to wick away sweat to keep you cool (or warm depending on the weather) and dry so you can have a comfortable run.

9. Come up with a race day nutrition and hydration strategy

Develop this plan weeks in advance so you can try it out on your long runs to see what works best for your body (especially your GI system) and when you should take a gel/salt tab to prevent dehydration, fatigue, and cramping. Your plan should include when and what to eat for breakfast before your run/race (I know this sounds obvious but you would be AMAZED at how many people refuse to eat breakfast before running 26.2 miles), when to take gels and/or sports drinks to boost your blood glucose levels during your run, and when to take salt tabs or electrolytes during your run to maintain hydration.

There are so many more tips I could share with you, but I think I will end it here. For more advice, you can always visit www.runnersworld.com as they are the experts in everything running and they recently published an article giving even more tips for how to run your best marathon, or send me a message via Twitter @TheDrRemmers and I will be happy to share more provide further advice in how to survive the marathon. Good luck and happy running!

Did you ran a marathon or preparing for one? Do you have tips to share?