Friday, September 30, 2011
Wednesday, September 28, 2011
Full of sarcastic, witty one-liners that accurately capture the over-whelmed feelings of over-worked graduate students, "Piled Higher and Deeper (PHD)" The Movie is a fantastic 75 min. experience. The movie was screened at the
campus on September 26th in front of an audience of approximately 450 to 475 – most of whom were graduate students – followed by a Q&A and book signing with Jorge Cham, its writer and creator of the online "PhD" comic strip that the movie is based on. Washington University
The clever editing and polished sound of the movie is amazingly the product of a cast and crew of graduate students, researchers, and others with connections to science. Even the series of professors who show up at the beginning are real faculty. The storylines sound familiar to many in the Ph.D. track. Cecilia is embarking on a Teaching Assistant position in hopes that this will strengthen her C.V. for a faculty position. She optimistically expects her students to be full of excitement and eager to learn. To her dismay, they aren't. Additionally, she is frustrated by not yet meeting her life goals of marriage and graduation. The movie also features "The Nameless Grad Student," the popular protagonist of the comic strip, who starts off the movie approaching many professors in hopes of joining their labs. He ends up doing a rotation of sorts in Professor Smith's lab and experiences incidents common to all graduate students – struggles with outdated machinery (as Prof. Smith would say, why spend money buying new equipment when you can waste countless graduate student hours?), pressures to produce data, and disheartening encounters with the formidable Prof. Smith who doesn't remember his name and responds to attempts at friendly conversation with comments like "Small talk is for small minds." Overall, the movie is just as funny and relatable as the comic strip; not a scene went by without at least a few appreciative chuckles from the audience.
Afterwards, Jorge Cham took questions from the audience and revealed many insights about the movie and his online comic strip. We learned that he went over his comics (first one written in 1997), found common themes that resonated through them (lab meetings, graduate students' love for free food, etc.), and compiled them together to make scenes for the movie. When asked how making a movie was different from producing the comic strips, Jorge responded that there are different expectations for a movie – audiences anticipate a developed narrative and perhaps surprises along the way, which is why he even revealed the name of "The Nameless Grad Student" in the movie, generating quite a bit of buzz among his fans. Interestingly, the name he chose for his protagonist is his father's name. During the Q&A and book signing, Jorge appeared to be very personable, chatting amiably with fans and staying late into the night to listen to many students' own stories of grad school when he must have been exhausted from traveling all day. He was very sarcastic and self-deprecating; his humor certainly translates to his strip. While introducing his film and asking members of the audience to raise their hands if they were undergrads or graduate students, he quipped that he wouldn't ask how many post-docs are in the crowd since they were already used to being ignored. However, when Jorge reflects on graduate school and his experiences traveling around the world speaking to graduate students – as well as the optimistic ending to his movie – it is clear that "Piled Higher and Deeper" is, above all else, meant to empathize and inspire hope. It allows us to laugh (and not cry) at the stressful situations encountered during graduate school and makes us realize that we are not going through the tough times alone.
Monday, September 19, 2011
Our MIDSCI reporter's blog on "The Discovery and Surprises with Natural Products" by Professor Erick Carreira at the UW-Madison Department of Chemistry Abott Symposium .
Natural products, secondary metabolites produced by biological sources, are often utilized as sources of novel small molecules for drug discovery. However, biologically-active natural products, such as the antifungal agent Amphotericin B (AmB), are of little use if they cannot be produced in quantities to meet patient demand. Many synthetic organic chemists have risen to this challenge by devising “total syntheses” of natural products from readily-available starting materials. Professor Erick Carreira has long been revered in his field for his total syntheses of stereochemically-complex natural products such as Macrolactin A and Erithronolide A and his use of challenging asymmetric bond forming reactions. In his seminar at UW-Madison’s Abott Symposium, Carreira outlined total syntheses of three natural products that associate with biological membranes, as well as structural analogs that were used to study structure-activity relationships (SARS). As a result of his work, Carriera has been able to draw conclusions about how these molecules behave in their natural settings.
AmB is the drug of choice for treating Aspirgillosis, a fungal disease most common in immune-compromised and cancer patients. AmB has a rigid, cigar-shaped structure and works by self-assembling into a transmembrane channel, causing electrolyte loss. Interestingly, the length of AmB and a typical fungal cell membrane are 20 and 40 Å, respectively; it has thus been hypothesized that the AmB ion channels consist of AmB subunits arranged in a head-to-tail fashion. It has been suggested that the hydroxyl groups on AmB could be essential to the activity of this antifungal agent should this head-to-tail arrangement be necessary for activity. Thus, Carreira set out to synthesize several deoxy analogs of AmB. The synthetic strategy involved synthesizing three components of AmB and combining them to form the final macrocycle. The syntheses of these AmB analogs revealed that the C35 hydroxy group is essential for activity—the C35 deoxy AmB analog was about 18 fold less active in S. cerevisiae as compared the parent AmB molecule. This suggests that the C35 hydroxy group is critical in forming transmembrane channels. Other work by Carriera and coworkers has shed light upon other AmB moieties necessary for activity; for example, the C2 hydroxy group on the mycosamine sugar is essential for antifungal activity.
Carriera outlined syntheses of other bioactive molecules and their analogs, such as the antibacterial guanacastepenes, and has been using his molecules to draw conclusions about SARS and modes of action, similar to his work with AmB. These types of strategies could allow for the modification and optimization of natural bioactive scaffolds to yield potent drug candidates.
Szpilman AM, Cereghetti DM, Manthorpe JM, Wurtz NR, Carreira EM. Synthesis and Biophysical Studies on 35-Deoxy Amphotericin B Methyl Ester. Chemistry—A European Journal 2009; 15: 7117-7128
Sunday, September 18, 2011
Currently at the Bernard Becker Medical Library at Washington University, a traveling exhibition, "Deadly Medicine - Creating the Master Race," is on display from the U.S. Holocaust Memorial Museum in Washington, D.C. Eugenics – "the study and practice of improving humans through selective reproduction" as defined in the exhibit – is the focus, with particular attention on the atrocities committed in its name during the Holocaust. It is a fascinating and deeply sad look at the effects genetics, medicine, and anthropology research have on the human population when science policies are misguided.
The exhibit, which will remain in town until October 30th, 2011, allows the viewer to learn a lot of information about the origin of the eugenics movement as well as the policies that grew from it. From either a desire to strengthen future generations' health and standing after WWI for Germany or prejudice and fear from rising immigration in the early 1900s for the United States, "positive" and negative eugenics arose, documented in the pamphlets, photos, and videos on display. In "positive" eugenics, public education campaigns were used to endorse maternal health or promote marriage and children (for the racially fit). "Ten commandments for choosing a mate" is a publication in the exhibit that exemplifies this. Negative eugenics is in the form of sterilization. A very interesting section focuses on eugenics in America, where we learn startling facts such as in 1933, 26 states had laws allowing sterilization based on eugenic reasons. When we arrive at the Nazi eugenics section, the pictures and videos of Jewish people, institutionalized Germans, or those deemed to be "subnormal" being studied or gassed can get quite emotional. It is rare for an exhibit to both increase our knowledge about a certain subject and move us on a deeper level, but this one certainly does both and is worth a visit.