Making Sense of Multiple Sclerosis Research (Blogroll)

(For a brief primer on multiple sclerosis, skip to the end of this article.)

March was National Multiple Sclerosis Awareness Month in the United States.

Kim and I at Bike MS 2013 with a Fighting
Shamrocks sign that sums up our feelings. Scientific
research is the only way to improve quality of life
for current and future MS patients.

Were you aware?

With any chronic illness, clear communication between patients, doctors, and researchers is a critical concern. Patients in particular, most of whom are scientific laypeople, have an extremely difficult time keeping up with developments in research. The multiple sclerosis (MS) community is no exception. Cutting-edge research is being conducted along a myriad of avenues related to MS, from the cause to the mechanism of disease progression to treatment development.

However, keeping patients informed of these cutting-edge developments in a way that is easily understood is a tough item for researchers. Blogging can help to change that by making research details available - and accessible - to everyone.

The Research Blogroll

Dr. Karen Lee, the vice president of research at the Multiple Sclerosis Society of Canada, keeps a blog detailing the major goals of studies funded by the Society (and more). In particular, this post builds understanding from the ground up to explain in layman's terms how three research teams are pursuing one facet of the MS problem.

It is easy to think of doctors, patients, and researchers as three mutually exclusive sets of people, but that is not always the case. In a series of posts entitled "MS Patient, Ph. D.," Dr. Griselda Zuccarino-Catania and Dr. Emily Willingham provide unique insights on all three realms based on their personal experiences both as scientists and as MS patients. They give information on everything from digesting exciting research findings to the frustrations of making sense of diagnoses from multiple doctors. The Multiple Sclerosis Discovery Forum, which hosts the series, is in itself an excellent resource for those interested in learning more about MS research.

Dr. Gavin Giovannoni of Barts and The London Neuroimmunology Group and another blogger by the name of MouseDoctor maintain a blog designed to keep the public informed of research findings across the MS community. If you are a biochemist looking for scientifically heavier reading material, then the blog is a gold mine for you. However, many of the posts are philosophical in nature and accessible to everyone, such as this post about how potentially harmful therapies fit in with the Hippocratic Oath.

We're All in This Together

A problem like MS requires minds to solve it, and not just a few. By improving communication between researchers and patients, just as these bloggers and many more are trying to do, the number of people in the huddle grows larger and larger. Improved communication carries a second benefit, however, which is articulated perfectly by the Multiple Sclerosis Society of Canada: "[...] Hearing directly from a researcher about their work provides a powerful tool of hope, of better understanding of what the future could promise through research."

---

About MS

Multiple sclerosis (MS) is a chronic disease in which a patient's central nervous system is slowly degraded. Specifically, the protective coating of myelin nerve cells is worn away, which throws a wrench in the body's communication systems. A wide variety of symptoms results, ranging from impaired memory to loss of motor skills. The National Multiple Sclerosis Society estimates that 400,000 Americans are afflicted with MS.

The cause of MS is not known. This fact makes researching possible treatments for the disease extremely difficult. For an excellent review of known trends in MS diagnosis, check out this 2008 paper in The Lancet ($). The National Multiple Sclerosis Society also offers this list of potential causes (read: research targets) for MS, along with a very interesting list of factors shown not to be the cause of MS.

Scientists of all sorts are involved in MS research. In particular, chemists and biochemists have developed several commercially available drugs that are used in MS treatment. These drugs can take the form of small molecules or large tailored antibodies; which drugs are applicable depends on how far the MS has progressed.

I Make My Pi with Silicon Nanowires

As this is the first Pi Day (3.14 ~ March 14) of Tree Town Chemistry's life, I felt that I would be remiss if I were to go through it without putting up a celebratory post. But what to write about?

Like any good chemist, I turned to my periodic table for answers. Element 3 is lithium. Element 14? Silicon.

Happy Pi Day, everyone. Let's make some batteries.

One Way Your Phone Battery Destroys Itself*

The lithium (Li) cycle for
the + electrode in a Li-ion
battery.

One of the classic problems in lithium ion batteries - the kinds of batteries currently powering your phone or laptop - is the instability of the compounds that make it up. The electrode materials in a lithium ion battery must be able to suck lithium ions out of the electrolyte while charge is flowing in one direction, and then spit them back out when the polarity of the battery is reversed (charging versus discharging). In a perfect substance, the process is totally reversible.

However, in most substances, the size of one crystal unit grows substantially during the lithiation process (see the cartoon at left). This causes the individual particles of the material to swell. The strain induced on the particles, either from the growth process itself or from bumping into neighboring particles, mechanically crushes the battery material. As a result, pieces of the battery material fall off of the electrode and are rendered useless.

This presents a huge problem for chemists and materials scientists. There are two main ways to look at it. One could imagine screening hundreds of compounds, looking for ones where the percent expansion during lithiation is as small as possible, thereby minimizing the strain. Another solution to the problem is to study exactly how these compounds expand, and then try to shape them on the nanoscale in such a way that the strain forces are minimized.

Silicon Solutions
Silicon is most famous for its applications in solar energy technologies, but it has also been identified as a lithium-ion battery anode (negative electrode) with record capacity for storing electrical energy. However, silicon also undergoes huge expansion once it accepts lithium ions - on the order of 400%. That fact makes it inapplicable to traditionally-structured lithium-ion electrodes.

A 2007 study led by Professor Yi Cui at Stanford University found a way around silicon's volume expansion. Professor Cui's research team developed a method of synthesizing electrodes composed of ordered silicon nanowires. The electrode structure is not unlike your toothbrush; each bristle is a silicon wire that is directly connected to the base of the electrode, called the current collector.

The unique electrode structure brings about two major improvements. First of all, the electrical conductivity of the entire electrode is improved, since all of the silicon is directly connected to the current collector. Secondly, the silicon wires have plenty of room to expand in length and in width without clashing against one another. Cui's team observed that their silicon nanowire electrodes exhibit record-breaking storage capacity and are stable over several charge/discharge cycles.

The result made an impressive impact in the battery community and is slated for limited commercialization soon. This paper is a great example of how materials chemists can solve problems by addressing concerns that fall outside of the chemical identity of the material. In this case, changing the shape of the material particles took an unimpressive substance and made it into something industrially relevant. And who knows? If these batteries are successful commercially, we might all be celebrating Pi Day with lithium and silicon in the future.

*Disclaimer: The pulverization issue is, of course, not the only method by which lithium ion batteries fail. There are many physical and chemical changes that take place within a battery cell as it is charged and discharged repeatedly, and each material presents its own special problems. Additionally, the anode is only one half of the battery, so there is still a lot of good research going on solving similar problems for cathodes as well.

If you're interested in reading more about nanowire electrodes, U of M researchers published a similar result using germanium nanowires in 2012. This research comes from the Maldonado group and the first author was Junsi Gu.

'Tis the Season for Tough Decisions

The acceptance letters are out, and students all over the country will be traveling from school to school to make sure they are as informed as possible when they make the decision. It's a big one - one that will set the stage for the rest of their careers.

The decision is where or whether to pursue a Ph. D. in chemistry.

Everyone approaches their decision a little bit differently, and to gain some perspective on that fact, I reached out to a few graduate students in the department and asked them about the factors they considered most strongly when making their choice.*

Department Size and Variety
All respondents agreed on one thing: when it comes to choosing a school, a big department with a lot of variety is always better. This idea is one that graduating students often haven't considered when they arrive for visitation. "A big program often offers a wider selection in terms of research, which I decided was critical in making my decision since I wasn’t 100% sure exactly what type of research I wanted to do [when selecting a school]," wrote Charles Lhermitte. Additionally, students aiming for spots in specific labs should acknowledge that there can be many other students vying for those spots, and the chances of not landing your first choice are real. A Ph. D. is a long and difficult degree, and if you get stuck working on a research project that you are not passionate about, it will be even more so. Choosing a school where there are several labs that are attractive to you makes having a good backup plan easy. Students also view schools that feature research rotations very favorably for the same reasons.

A varied department also offers a safety when it comes to student/advisor relationships. As graduate students, we're offered the somewhat unique opportunity of choosing our boss, and in many ways choosing the right advisor is just as critical as choosing research that you are passionate about. "One advising style is not right for all graduate students and can lead to 5 long and miserable years," writes one respondent. "I'd recommend really talking to professors and asking students about advisor/student relationships and mentor styles."

Program Rank
Each student considers the prestige of a school's program when deciding whether or not to apply there, and program rank is just as important in the final selection process. An advanced degree from an elite institution is certainly a lofty goal, and building one's academic pedigree in that way has obvious benefits when it comes to landing a great job after graduate school. The Ph. D. is a huge investment of time and effort. Everyone wants to get a job that makes that investment worthwhile.

However, some respondents viewed rank as a less important consideration when reviewing their decision process in retrospect. Choosing a school based on rank alone is risky. Be sure to weigh program rank carefully against other factors such as those outlined above.

Personal Factors
"I like to be involved in where I live, so it was important that there are opportunities for that," writes Kim Daley. Visitation weekends just as much about getting a feel for the research as they are about experiencing the town surrounding the school, the social atmosphere of the department, and your potential lab mates. It is important to find people that you can get along with. Additionally, the other members of the department will turn into your mentors and collaborators, so it is worthwhile to check your own work habits against theirs to see how they mesh. "Fitting in with a group is semi-important since so much time is spent in the lab. Work style and work ethic are important," notes one respondent.

Moving on to graduate school usually means packing up and shipping off to a new part of the world, and for students in relationships, that can be especially stressful. There is a lot of pressure to make a decision that is in the best interest of your professional life. "However," writes Daley, "your personal life is also important. When I was picking, I felt like considering my boyfriend would somehow make me a weak person. But it's okay."

School or Work?
For some students, the decision involves not only choosing between graduate schools, but choosing between graduate school in general or entering the workforce directly. Working for a few years after undergrad can provide invaluable experience and perspective, especially for those just looking to take a break before returning to advanced education later on. (And, of course, the pay is often significantly better than a graduate student stipend.) Working in industry can also win you contacts and references that distinguish you from other applicants when applying for future positions.

For those with aspirations of managing research projects, however, a Ph. D. is undoubtedly the way to go. "Those with a B.S. may hit a sort of promotional 'ceiling' a lot sooner than a Ph. D.," writes Lhermitte, who interned at Procter & Gamble before applying to graduate school. "I discussed this with my bosses and they agreed that a Ph. D. would allow me to move more quickly up the ranks in the company. If you want to go far in a technical company, then you have to get a Ph. D." Managing a research project is a skill that must be learned like any other. Over the course of a Ph. D., you will not only gain focused knowledge and become an expert in your field, but you will also develop your skills as a manager of research - training that is very difficult to find elsewhere. The Ph. D. is a certification of that training.

It's Your Decision - Nobody Else's!
Choosing what to do after getting your undergraduate degree is a big professional decision, and it is necessarily stressful. That stress can be compounded by other figures in your life - parents, undergraduate advisors, etc. - telling you what is and is not important in a school. To some extent, their advice is necessary to help inform your decision, but remember that the final decision is yours alone. Your choice should reflect the best compromise among all of the factors that are truly important to you, no matter what those factors are.

*comments lightly edited for clarity

P.S. Thank you to everyone who responded for this post! Input like yours makes these kinds of pieces possible. Showcasing student opinion is an important part of the project for me. If you have more to add, feel free to leave a comment!

Chemistry Literature Feature Vol. III

Have you seen a good paper lately? Written one? Send it in and have it featured here! treetownchem@gmail.com

In this episode of the Tree Town Chemistry Literature Feature, we'll have a look at porous crystals that take water vapor out of gases, the chemistry of photoexcited melanin, and a real-time picture of how one kind of nanoparticle transforms water to oxygen.

But first, a thought we've all had, but everyone was too chicken to say out loud (except one person):

Overheard at Michigan
   "2% yield? This sounds like a pretty expensive reaction."
   "Well, considering we borrowed half the chemicals from other groups, it's not expensive for you."

Analytical: Applications of Convolution Voltammetry in Electroanalytical Chemistry
 With a growing focus on the development of ionic liquids for various applications, the authors of this Analytical Chemistry (ACS) paper point out that some conventional electrochemical techniques are inapplicable in highly viscous media. The authors explore a technique called convolution voltammetry and test their technique against known data for a variety of systems. The method is validated by their experimental data. Importantly, the technique does not depend on physically mixing the analyte solution, which makes it quite versatile.

Chemical Biology: Multidimensional Profiling Platforms Reveal Metabolic Dysregulation Caused by Organophosphorous Pesticides
In this study, published in ACS Chemical Biology, the authors design and explore a screening protocol in hopes of investigating the effects of pesticides on metabolism in mice. The results of the screening show that more than 20 proteins are inhibited by the phosphorous-containing pesticides. The inhibited proteins (serine hydrolases, for the most part) are connected to lipid metabolism and linked to several diseases - surprise, pesticides are still bad for you!

Inorganic: Time-resolved observations of water oxidation intermediates on a cobalt oxide nanoparticle catalyst
Discovering substances that efficiently oxidize water is a hot issue in research in alternative energy (see water splitting). A recent paper in Nature Chemistry (NPG) investigates the intimate mechanism of water oxidation over nanoparticle catalysts using time-resolved vibrational spectroscopy. The authors are able to provide direct experimental evidence for several intermediates in the catalytic cycle; such investigations are notoriously difficult (and thus rare) for heterogeneous systems, making this paper a must-read for anyone in the field.

Materials: Microporous Coordination Polymers as Efficient Sorbents for Air Dehumidification
Microporous coordination polymers are composed of interconnected metal ions and organic linkers, forming crystalline networks that can have huge pores (molecularly speaking). This study, published in Langmuir (ACS), demonstrates the power of microporous coordination polymers as dehumidifying agents. The authors conclude that, due to their intrinsically large surface areas and ability to regenerate with low energy input, microporous coordination polymers are an attractive alternative to conventional dehumidifying agents.
-University of Michigan research from the Matzger Group

Organic: Iridium-Catalyzed, Intermolecular Hydroamination of Unactivated Alkenes with Indoles
This Journal of the American Chemical Society paper details the reactivity of a new organometallic iridium catalyst towards olefin substrates. The catalyst combines the olefin with indole to create new alkylamines in good yield. Working with unactivated olefins is advantageous in that it can reduce the amount of chemical modifications necessary to achieve a given product.
-suggested by Emilia Groso

Physical: Near-Infrared Excited State Dynamics of Melanins: The Effects of Iron Content, Photo-Damage, Chemical Oxidation, and Aggregate Size
Melanins are the molecules that give your skin its color, and are also responsible with providing some protection from ultraviolet light from the sun. However, in some melanomas, it is believed that a melanin aggregate in its excited state (after absorbing light) may actually make the cancer worse. In this study, published in the Journal of Physical Chemistry A (ACS), the authors investigate how melanins behave after light absorption in both free and aggregate form by ultrafast pump-probe spectroscopy.
-suggested by Kim Daley

Physical chemistry aficionados may also enjoy the Inorganic paper, which involves time-resolved studies of catalysis over cobalt oxide surfaces.

Remember, if you come across an article that you think should be featured here, send it in! treetownchem@gmail.com

ACS - American Chemical Society
NPG - Nature Publishing Group