New year's resoultions from scientists

Resolutions from the Bench

 

and some science to help you make your own!

Compiled and written by Evelyn Litwinoff and Katherine Peng

Like many of us out there, you may deem a New Year’s resolution a successful one if it lasts through January. To help create your own, the Scizzle staff is offering some tips backed by neuroscience (plus some science-y examples) that may help you to finally follow through in 2015.

 

Tip #1: Give yourself a pep-talk

Positive self-reflection boosts serotonin levels which is essential for proper functioning of the prefrontal cortex. The prefrontal cortex is our impulse control and decision making center, and plays the additional role of giving flexibility to habits ingrained in the basal ganglia. For example, subjects lulled into a conversation about their positive qualities prior to reading an informational packet developed a greater intention to quit smoking or eat healthier.

 

For inspiration, see this positive worded resolution (“I am!” “I will!”):

[quote]I am going to work on becoming better at networking. I will go to more networking opportunities, and I will not spend all of my time talking only to people that I know.[/quote]

S.S., Industry Research Scientist

 

Tip #2: Focus on one or few goals

Baumeister et al. have shown over and again that willpower is a limited resource. The effort it takes to complete one goal may render us too exhausted for the next. In fact, willpower depends on glucose levels, and a good dose of glucose helps to counteract willpower depletion (though admittedly not so helpful if your resolution is a diet).

[quote]This year, I will focus on the "existing" rather than "imaginary" problems in science; and I will try to address those by my solutions. The focus of the year will change from "providing solutions" to "identifying the right problems.[/quote]

Padideh Kamali-Zare, a new science entrepreneur and a Scizzle blogger

 

Tip #3: Give yourself a distraction

In a well-known series of marshmallow experiments, children were promised more marshmallows if they could resist the one marshmallow they were left in a room with. The most successful kids distracted themselves with singing or playing, and as a bonus had better SAT scores later in life.

[quote]For 2015, I will dedicate time every day to step away from the bench/paper I’m reading/experiment I’m designing to take a mental break, even if it’s only 5 or 10 minutes long. And I promise not to go on Facebook during those breaks![/quote]

E.L., Immunologist

 

Tip #4: Remind yourself

That the feeling of being in control is inherently rewarding. Imaging has shown that subjects making choices in which they control the outcome have greater activation in structures of the brain involved in reward processing.

 

[quote]For New Year's, my resolutions would be to 1) Actually finish one of those online statistics classes so I understand the statistical tests I will eventually be using to analyze my data (I keep starting the courses and then getting distracted and stopping about halfway), and 2) Come up with a better system to consolidate, organize and keep track of my paper reading/notes; currently things are spread across notes in PDF files, hard-copy notes, and Google Documents.[/quote]

- Susan Sheng,  neuroscientist and a Scizzle blogger

 

[quote]Read a paper a day (or at least an abstract) and be more efficient.[/quote]

– K.Z., neuroscienctist

 

[quote]My science New Year's resolution is to learn tissue culture techniques. And also, to be more careful with the ethanol around an open flame so I light fewer things on fire.[/quote]

E.O., Postdoc

 

Have a wonderful happy new year!!!

 


How I Nailed My Lab Rotation and Got in the Lab I Wanted

 

By Evelyn Litwinoff

From the first time I met with my now PI to discuss a possible rotation, I knew I wanted to end up in her lab. She took me seriously even as a lowly first year grad student, and valued my thoughts and input on the rotation project we discussed. I left that meeting super excited about the rotation to be, and I couldn’t wait to get started.

 

Arguably the best part about this rotation was that I made and had my very own project as a rotation student that had the possibility to become a thesis project if – I mean when – I joined the lab. And the project was all about autophagy – a topic I had been introduced to in undergrad, found super exciting, and wanted to learn all about. (A quick refresher: Autophagy is a cellular recycling mechanism used to degrade large proteins, organelles, aggregates, and other substrates. It is essential for cellular health, especially in times of starvation. As Bill Nye the Science Guy would say,Now you know!”)

 

Step #1: Taking initiative

 

I came in on day one ready to generate tons of data, eager to become friends with everyone in the lab, and “wow” them all with my super science skills. Then I hit roadblock #1: the person in the lab I was assigned to work under wouldn’t let me do anything myself. I would watch her as she plated the cells, changed the media, dissected the mice, etc, and all I was able to do was label tubes. Not exactly how I imagined this rotation would be. But instead of sulking around wishing things would be different – ok after doing that for 2 weeks and spending time looking up other labs to rotate in – I spoke with another post-doc in the lab, and she agreed to have me work with her instead. Later after I joined the lab, I found out from this post-doc that by taking charge of my situation and changing it for the better, I showed her (and therefore my PI) that I really wanted to be a part of the lab and I could take initiative with my own project.

 

Step #2: Learning and mastering new skills – Evelyn vs. the Western Blot

 

My undergrad research was all about Caenorhabditis elegans (C. elegans) genetics, so most of my science skills before grad school consisted of PCR, running DNA gels, sequencing, and C. elegans specific handling. Hence, I had never done a western blot myself before this rotation. But by the end of my 3 months in the lab, I was a western blot master! One of the main ways to assess if autophagy is upregulated is to look for increases in the autophagy specific protein, LC3. So the end points of all my cell culture experiments were western blots for LC3 and another autophagy specific protein, Beclin. I worked my butt off doing western blot after western blot, sometimes staying in lab until 1am, and was able to have new results at almost every meeting with the PI. At the end of my rotation, one of the research associates came up to me and said, “I can’t believe how much data you generated in such a short period of time.” I was very proud of how much data I was able to produce, but more importantly, I was happy I learned this new skill quickly enough that I didn’t have to take up a lot of my post-doc’s time when running my own experiments.

 

Step #3: Being a good labmate

 

When I used up my post-doc’s stocks and buffers, I always asked her for the recipe to make more, and I replaced whatever I took. Same thing goes for refilling the pipettes in the cell culture room, emptying the vacuum, etc. Doing these types of lab chores goes a long way in showing your commitment to the lab, and in convincing everyone that they want you to stick around. I didn’t realized how important these small things were until I joined the lab and saw everyone’s reactions to the, let’s say “absent-minded” summer students.

 

Step #4: Admitting mistakes

 

At one point in my rotation, I left some antibodies on the bench overnight. Major whoops. I apologized profusely to my post-doc. Although she was not happy with me, she understood it sometimes happens to everyone and appreciated my straightforwardness in telling her.

 

Step #5: The big finish!

 

One of the things my PI from undergrad engrained into my head was how to make a good presentation. She would never be happy with my slides until they were mostly pictures with very very very few words underneath. I used these skills to put together a presentation for the end of my rotation. In my now PI’s words, “Evelyn, these slides are gorgeous!” Cue the inner Cheshire cat grin. I left that rotation with good impressions on the lab and the PI, and I kept in touch with the post-doc I worked closely with. Sometime in the middle of my next rotation, I emailed this PI and asked to join her lab. To my delight, she said yes!

 


Yoda and the Science of Aging in the Star Wars Universe

 

By Evelyn Litwinoff

 

The first time I saw the Star Wars movies, I could not take Yoda seriously. Having grown up watching and loving the muppets, Yoda sounded too much like Fozzy Bear to be a Jedi Master. I kept waiting for him to add “wakka wakka” to the end of his nonsensical sentences and break out into song and dance.

 

If you think about it, Yoda is certainly an interesting creature. His species is never defined, we don’t know much about his childhood background, he has a crazy long lifespan, and he’s two feet tall yet a powerful fighter. So as homage to Yoda from a scientist’s perspective, I’d like to play a game with you. Let’s pretend Yoda lives in our universe and use our science prowess to figure out how on earth, excuse me, on Dagobah, he lived to be 900 years old without getting cancer.

 

When thinking about mechanisms behind aging, the first thing that comes to mind is telomeres. A telomere is a non-coding DNA sequence that serves as a protective “cap” on the end of a chromosome. (A chromosome is essentially a condensed string of DNA.) Every time a cell replicates it makes a copy of its DNA to pass on to the new cell. However during the process of replication, the new DNA copy loses some of the sequence on the end of the chromosome. In order to prevent losing important DNA sequence, the telomere sequence comes after the important DNA sequence so it is the telomere sequence that gets shorter with each replication. When telomeres become too short, which is usually by the end of the organisms’ lifespan, the cells are considered old and will die, eventually resulting in the death of the whole organism.

 

This leads us to idea #1: Yoda must have super long telomeres so it would take centuries for these telomeres to shorten and cause death. This issue with this hypothesis is that absolute length of telomeres does not necessarily correlate with longer lifespan. For instance, mice telomeres are longer than humans telomeres, but mice have a lifespan of 3-5 years, which is way shorter than human lifespan. Vera et al suggested that instead of telomere length, rate of telomere shortening more accurately correlates with lifespan, i.e., the slower the rate of telomere shortening, the longer the lifespan. So let’s alter idea #1 to idea #2: Yoda had super long telomeres with a super slow rate of telomere shortening.

 

Now telomeres can be elongated by the enzyme telomerase. So it would be possible that in addition to having long telomeres with a slow shortening rate, Yoda could also have high levels of telomerase. However, overexpressing telomerase in mice leads to the development of cancer, and as far as I know, Yoda didn’t have any tumors or chemotherapy during his lifetime. Interestingly, there is a body of literature on telomerase in cancer resistant mice. How fascinating is that! These cancer resistant mice have a mutated tumor suppressor gene, p53, which prevents development of cancer cells. In this cancer resistant environment, telomerase overexpression leads to a longer, healthier lifespan.

 

This led me to wonder, do any species have naturally occurring mutations that make them resistant to cancer (and would this species be similar to Yoda)? Scizzle to the rescue! Apparently, naked mole rats have fibroblasts (cells that produce fibers such as collagen) that secrete cancer killing signaling molecules, which makes these mole rats resistant to cancer! (For those interested, they took the media from cultured naked mole rat fibroblasts and used it to culture breast cancer and liver cancer cells. These cancer cells were unable to survive with the mole rat fibroblast media, although they did survive with media from cultured mouse fibroblasts.) So what is different about these naked mole rat fibroblasts? Although the mechanism of cancer resistance is not fully worked out, it is known that there are mutations in the naked mole rat p53 gene that increase DNA repair mechanisms and cell cycle arrest, but promote apoptosis (cell death). These mutations are believed to have evolved to promote survival in hypoxic (low oxygen) environments, where naked mole rats live.

 

Let’s bring this back to Yoda. If Yoda’s lifespan is due to long telomeres with a slow rate of telomere shortening, it is possible that Yoda has constitutively active telomerase in order to keep the telomeres in tact. However, if he had high levels of telomerase and no signs of cancer, he must also be cancer resistant. Since we just learned that naked mole rats are naturally cancer resistant and this may be related to their hypoxic environment, could Yoda’s environment make him cancer resistant? Towards the end of his life, Yoda lives in a swamp: definitely not a hypoxic environment. Furthermore his end of life environment wouldn’t explain how he survived all those years before arriving to Dagobah. Since we don’t know all that much about Yoda’s childhood, let’s get creative here. We do know that Yoda lives and breathes with the force just like the rest of his species. So maybe the force is a stream of hypoxic energy that altered his species’ genes to make them cancer resistant. This fits well with the fact that all members of his species we know about are Jedi, and Jedi are known to have longer lifespans.

 

Our study of Yoda and telomeres gives us an idea of how Yoda lived to be 900 years old without developing cancer. Of note, this discussion is based on the major motion pictures, not the Expanded Universe. But, if you are well versed in this expanded media franchise, I’d love to hear your scientific take on aging in the Star Wars universe!

 

 

 


Can a Mutation Protect You From Diabetes?

 

Evelyn Litwinoff

For the first time in diabetes research history, researchers have found mutations in a gene that is associated with a 65% decrease in risk of developing type 2 diabetes (T2D).  What’s even more astounding is that only one copy of the gene has to be mutated to show this protection.  The gene of interest is SLC30A8, which encodes a zinc transporter in pancreatic islet cells.  (A quick brush up on your cellular anatomy: Pancreatic islet cells produce insulin, which the body uses to uptake glucose into cells.  Zinc plays an important role in the uptake, secretion, and structure of insulin.) This study found not 1, not 2, but 12(!) different loss-of-function mutations, all in SLC30A8 and all predicted to result in a shortened protein, that associates with protection from T2D risk.

 

Most of this study is based upon sequencing genes that were previously associated with a risk of developing T2D.  Overall, the authors looked at about 150,000 individuals from various ethnic populations in order to obtain statistical significance for their associations.  Their results are surprising since previous studies had linked mutations in SLC30A8 with an increased risk of T2D.

 

However, this study does not address how a decrease in function of the zinc transporter, named ZnT8, could lead to protection from a disease state.  The authors did conduct one mechanistic-ish experiment, but this was only to see if the mutations in ZnT8 actually affect the activity of the protein.  To this end, the authors overexpressed 4 different mutated versions of ZnT8 in HeLa cells and saw a decrease in protein levels in 2 out of the 4 versions.  Furthermore, they showed that the increased protein degradation could be part of the reason for the observed decrease in amount of protein.  Their main conclusion from these cell experiments show that some of the mutations in ZnT8 result in an unstable protein, which would help us understand how the zinc transporter is not working, but it does not explain why the dysfunctional protein protects from T2D.  Hopefully, this paper will spark others to investigate a mechanism for the associated protection.

 

Currently, Pfizer and Amgen are starting to develop drugs that mimic this mutation to see if they can replicate the protection.  Although a new diabetes drug based on this study could be 10-20 years down the road, this study still makes a big splash in the diabetes research community.


Tag, your turn! - Developments in Contraception for Males

 

By Evelyn Litwinoff

With Valentine’s Day behind us, let’s talk about a more detail-oriented part of relationships: contraception.  The pill, the ring, the patch, the shot… there are so many choices for women to choose from when it comes to picking their contraception.  But for guys?  Condoms, withdrawal (or “pulling out”), and sterilization are their main options, and what dismal options those are.  The effectiveness of women’s contraception far exceeds the options available for men, so no wonder the responsibility tends to fall more on women. Wouldn’t it be great if a high-efficiency contraceptive method existed for guys so that the responsibility for contraception could be more equally shared?  This would not only make a difference in first-world countries where pharmaceutical companies could profit from this type of drug, but it would also help developing countries where there are high rates of maternal death from unsafe abortions and other complications of unwanted pregnancies.

Most contraception options on the market today are based upon the first advances from the mid 1900s, namely the pill and intrauterine devices for females.  These methods are all centered on inhibiting ovulation or interfering with the menstrual cycle.  Methods of contraception for males date back to the 5th century BC where men would soak their testicles in a hot water bath to prevent conception.  Despite this heat-shock technique being far from fool-proof, it is still recommended today in conjunction with other physical barriers. Furthermore, many male hormonal and steroidal drug options have serious side effects, such as irreversibility and loss of libido, which are definitely counterproductive for a contraception device.

However, recent advances in this field may change all that.  In 2012 Matzuk et. al found a small molecule inhibitor, JQ1, that inhibits BRDT, a protein essential for spermatogenesis.  Wild-type mice that lack BRDT are sterile, making it a compelling target for contraception development.  Their mating studies show that the contraceptive effect of JQ1 is dose and time dependent, meaning that treatment with JQ1 will only result in sterility while the drug is administered.  Furthermore, JQ1 does not adversely affect testosterone levels, mating behaviors, or offspring viability.  Taken together, this makes JQ1 an exciting possible drug choice for further development.

I did a quick search on Scizzle to see if anything new had been published on the JQ1 front, but I found more on JQ1 as a possible cancer drug rather than a contraceptive device.  Obviously the effects of JQ1 would need to be studied in humans before a pill could become available.

A Google search on male contraception led me to a different type of approach.  Instead of pursuing an oral drug, the Parsemus Foundation is developing the polymer gel, Vasalgel, to block sperm transport. Vasalgel would be injected into the vas deferens instead of cutting this organ as in a vasectomy.  Then if and when the man decides he wants to have children, the polymer can be flushed out with another injection.  Vasalgel is still under development in the US but the first clinical trials are projected to begin by the end of this year.

It will probably be a few, OK many more years before we see a male equivalent birth control pill on the market, but this is certainly an exciting area of research!

If you’re interested in learning more, check out the Male Contraception Information Project at http://www.newmalecontraception.org/