science

Chromatography and “Air Traffic Control” Interplay Direct Olfactory Function

Posted on by Anupama Gopalakrishnan

It is not difficult to appreciate why a keen sense of smell is important to well-being and to general living. While it signals the presence of delicious (or stale) food before we can even see or taste it, it has obvious great survival value to be able to alert living beings of danger such as certain poisons, leaking gas or fire. Humans are known to identify about 10,000 different types of odors. Of course dogs have vastly improved and keener sense of smell than human beings.

When odorant molecules (molecules that we can smell) reach the nostril, they dissolve in the mucus and bind to olfactory receptors present on the cilia of each sensory neuron. This binding activates a G-protein coupled cascade involving adenylyl cyclase. This causes the release of cyclic AMP and opening of cAMP-dependent sodium channels. Influx of sodium causes the membrane to depolarize and activate an action potential for propagation of the signal to the brain where it is analyzed and decoded(1). This seems pretty straightforward until one realizes the sheer magnitude of smells we are able to identify using this mechanism. Continue reading “Chromatography and “Air Traffic Control” Interplay Direct Olfactory Function”

How Is a Molecular Biologist Like a Computer Programmer?

Posted on by Maciek Smuga-Otto

My wife, the molecular biologist, tells me she spends her days “at the bench” and “in the hood.” There, she works with cells, plasmids, RNA, enzymes and buffers, incubators, water baths, columns, gels, filters and spectrophotometers. She transfers various quantities of liquids into and out of plastics and glassware. At least, that’s what I understand when I ask her, “how was your day?”

I can’t really understand her fascination with all of this, but then I don’t have to: I’m an app developer, a programmer who designs and builds applications for smartphones and tablets. My work day consists of sitting in front of a laptop, cranking out code. There’s the occasional break afforded by meetings and presentations, writing up design documents, sketching out how a user interface might look like. Then it’s back to the computer, and programming.

But in spite of these differences, there is a critical aspect of my wife’s work that, whenever she speaks of it, I immediately recognize in my own professional life: We both rely extensively on kits and components, and doing so profoundly affects the way that we approach our jobs. Continue reading “How Is a Molecular Biologist Like a Computer Programmer?”

Cancer research yields unexpected results

Posted on by admin

Louis Pasteur once said “Chance favors the prepared mind”. Surely any scientist can attest to this. Discoveries of things  like artificial sweeteners, Teflon, and penicillin were all unintended products of unrelated research. Recently, scientists at the Duke Cancer Institute studying the microevolution of enzymes involved in cancer happened upon a missing enzymatic link in a very unrelated area of research that has less to do with cancer than with the production of carpeting, apparel, and auto parts(1).

Nylon is a critical component in all of those products, any many, many more. Production nylon requires a compound called adipic acid. This intermediary, one of the most widely used chemicals in the world,  is produced from fossil fuels and pollution released from its refinement process is a leading contributor to global warming. To date, there hasn’t been a “green” way of producing adipic acid because there is one critical enzyme in the synthesis pathway that isn’t available: 2-hydroxyadipate dehydrogenase.

Biochemical engineering on its own had not produced a sufficient dehydrogenase to do the job. Enter the cancer researchers.   Cancer involves the microevolution of cells which offer benefits to the cells, sometimes including gain-of-function mutations in metabolic enzymes. Duke researchers identified a  mutation in glioblastomas that alters the function of isocitrate dehydrogenase. The Duke team applied their knowledge of how enzymes change during cancer to lay the blueprints on a new method for producing  clean, green, adipic acid. By using the same mutation framework, the scientist found that they could create enzymes from homoisocitrate dehydrogenase found in yeasts and bacteria that were capable of producing adipic acid from inexpensive sugars. The group still needs to scale up their production, a process that will still require a tremendous amount of work.

1.  Reitman, Z. et al. (2012) Enzyme redesign guided by cancer-derived IDH1 mutations.  Nat. Chem. Biol.  Available online.

Endo H Application: Monitoring Protein Trafficking

Posted on by Gary Kobs

Endo H (Endo-ß-N-acetylglucosaminidase H) is a 29,000 dalton protein with optimal activity between pH 5 and 6. In contrast to PNGase F, which cleaves all N-linked glycans at the site of attachment to Asparagine (Asn), (with the exception of those with fucose attached to the core GlcNac moieties), Endo H hydrolyses the bond connecting the two GlcNac groups that comprise the chitobiose core (see Figure 1.). In addition, Endo H cleaves high mannose and hybrid glycans, whereas complex glycans (those with more than 4 different sugar types per glycan chain, including the GlcNac groups) are resistant to hydrolysis.

The unique specificty of Endo H and PNGase F can be used to monitor protein trafficking. Basic N-Glycosylation occurs in the endoplasmic reticulum. Proteins in this stage are sensitive to Endo H digestion. If proteins have entered the Golgi body where additional modifications occur to the glycan, they are resistant to Endo H digestion.

The following references illustrate this application:

A Scientist’s Rant about the Word “Theory”

Posted on by Terri Sundquist
Frustrated scientist

I have many pet peeves in my life. Because I am a scientific editor, many of my pet peeves revolve around abuse of the English language. The abuse that set me off most recently is the misuse of the word “theory”. These days everyone has a theory about something. For example I have a “theory” as to why I gained five pounds over the holidays: Too much rich food and egg nog! However, from a scientific standpoint, saying “I have a theory as to why I gained five pounds over the holidays” is not a proper use of the word theory. While it is likely that the food and egg nog contributed to the weight gain, I do not have a theory. The cause of the weight gain has not been scientifically scrutinized and put through rigorous testing. There isn’t a pile of scientific evidence to support my statement. What I have is a sound working hypothesis, not a theory.

Continue reading “A Scientist’s Rant about the Word “Theory””

Odyssey of a Grad Student and the Playlist that Paved the Way

Posted on by Karen Reece

Grad school is no walk in the park. Whether the topic is English or Astrophysics, most grad students would agree that the journey to the coveted PhD can simply be described as “hard”- academically, financially, mentally. It is very important to have an outlet for the associated stress such as a hobby or exercise. My outlet was music. Music is very important in my life. It is so important that most people close to me have their own soundtrack that plays in my head when I think of them. Needless to say, music played a big part in saving my sanity during my 7.5 years in grad school. As time went on, there were several songs that marked important milestones and emotions I experienced along the way. When I defended my thesis, I decided to leave the department with a musical story of how I made it through. I created a compilation CD of all these songs to share with the department and any other struggling grad students I encountered. The CD has a custom label featuring the structure of the protein I studied, cardiac troponin C.

In this blog, I will share with you that playlist, entitled “Odyssey of a Grad Student,” and a description of the significance of each track. You can listen to all but one* of the songs on YouTube (http://youtu.be/8qrriKcwvlY). Click the link and listen as you read along. Continue reading “Odyssey of a Grad Student and the Playlist that Paved the Way”

Slightly More than Half of Everything I Am Is Thanks to You

Posted on by Sam Jackson

In honor of Mothers everywhere, we are unashamedly recycling this post because it’s just that good.

Analogues

Posted on by Sam Jackson

People who know me well have, at some point, heard me hold forth on the subject of Antarctica. It’s a passion of mine, though I’ve never been there. The forgotten continent is like the Sirens, pulling those who dare to trespass upon the ice back to one of the bleakest places on Earth.

I have consumed many accounts of life there, and have configured my internet services to deliver me news reports that deliver little crumbs of information. Anything that mentions Antarctica crosses my screen.

My fascination derives from boyhood dreams of space. Young visions of piloting starships and traversing Martian landscapes – visions of adventure, glory, and alien encounters – shattered in daylight on a January day in 1986 as I sat cross-legged on an elementary school gymnasium floor. It would be years before I saw 2001: A Space Odyssey, but watching the Challenger disintegrate into a fiery end, I immediately understood one of its central lessons: space is not glamorous, glorious, or any more alien than many of the places on our planet. Space is cold, unemotional, and unforgiving. It is intolerant of error, and it is lonely. And despite these things, it is where any future humans can hope to have must lie.

I will never go into orbit, but Antarctica, that’s the next best thing. Cold. Unforgiving. Intolerant of error. Nearly devoid of life except that which we import and resupply, it is where we troubleshoot the logistical problems of sustaining remote and isolated human colonies. Having spread across six other continents, it is our last terrestrial frontier.

No, I will never float among celestial bodies and listen to the low murmur of the universe rippling deep in the dark silence of space. But there is another place where we pursue science, a place closer to home, where I can be cold and alone and maybe catch a stray shard of a broken childhood dream.

OK, I’ve Got My Degree. Now What?

Posted on by Terri Sundquist
One of many alternative science careers

Years ago, when I was in graduate school studying molecular biology, many of my professors seemed to place a lot of value on the traditional career path: several years of post-doctoral fellowships, followed by a career as a tenured faculty member at a big academic institution, with teaching responsibilities and a laboratory, post-doctoral fellows and students. At the time, many of my fellow students and I planned to follow this path and, eventually, become primary investigators and manage our own labs. There was little talk of other career choices. However, after several years of graduate school studies, I realized that, as much as I enjoyed learning and thinking about science, certain aspects of spending 3–6 years as a “post doc”, then managing my own lab and writing grants did not appeal to me. I had to revisit the question “What do I want to be when I grow up?”

So, what else could I have done with my science degree?

Continue reading “OK, I’ve Got My Degree. Now What?”