Cystic fibrosis is an incredible example of a truly molecular disease. It’s caused by mutation of one gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that helps maintain salt homeostasis in epithelial cells. Epithelial cells line surfaces and cavities of our bodies, things like the airway, sweat glands, and ducts in the liver and pancreas; these cells stick close together to create barriers between different environments and maintain a careful balance of fluid and electrolyte shuttling between these environments. CFTR transports chloride and other anions into mucus lining the epithelium, and sodium and then water follow to maintain normal, fairly fluid mucus. If CFTR is dysfunctional, the balance breaks down; thick mucus builds up in passages of the airway and digestive system, which become blocked. The obstructions alone cause serious respiratory and gastrointestinal problems, but the thick mucus in the airway also creates a cozy home for bacteria, setting the stage for respiratory infections. The mucus and associated complications significantly impact quality of life, but it’s the infections that typically kill.

Schematic of CFTR structure from CFTR.Info

CFTR is a massive and complex protein, that must be properly folded, embedded in a membrane, and shuttled to the cell surface. The fully functional, or mature, form weighs in at almost 190,000 Daltons (g/mol for the chemists out there ), which is more than 3 times the size of a typical protein. It’s initially expressed as a smaller precursor protein (~135,000 Daltons), but as CFTR passes quality control checkpoints, it’s decorated with sugar chains that tell cellular machinery that this CFTR protein is OK and ready for the next step of the process. With normal CFTR, only about 30% of CFTR that’s expressed actually transits the checkpoints successfully. The remaining protein is trashed without ever having done the job it was made to do. Just as sugars flag proteins that have passed quality control, ubiquitin commonly flags proteins that need to be degraded. Ubiquitin is a small regulatory protein that can be attached to a specific group (lysine) on other proteins. Ubiquitin can be conjugated to itself to create poly-ubiquitin chains, which target the proteins to the proteasome, a large multi-protein cylinder that cuts proteins into smaller pieces, or to the lysosome, an acidic intracellular sack filled with degradative proteins; in both cases, the end result is destruction of ubiquitinated proteins. At  Experimental Biology 2013, Dr. Seakwoo Lee, a research fellow in Pam  Zeitlin’s lab at Johns Hopkins Children’s Center, presented work on how ubiquitin modifies and regulates CFTR stability.

Two ways to ubiquitinated protein degradation (source)

The Zeitlin lab worked with Michelle McClure in Eric Sorscher’s lab at the University of Alabama at Birmingham to use mass spectrometry (“mass spec” to its friends) to identify residues of CFTR that had been modified by ubiquitin used. CFTR was isolated from cells and chopped into smaller fragments; this process removes ubiquitin but leaves behind a trace of it (glycine-glycine) where the ubiquitin tag once resided. Mass spec defined the amino acid sequences of fragments and the locations of glycine-glycine modifications and thereby ubiquitin. Lee mutated each glycine-glycine tagged site to arginine, a substitution that maintains the charge of the protein but that cannot be modified by ubiquitin. For each mutant, he looked at the protein expression levels of total and mature CFTR. He determined whether ubiquitination of each lysine targeted CFTR to the proteasome or the lysosome by using small molecule inhibitors. Because CFTR only functions at the cell surface, Lee  checked surface expression of the mutant by confocal microscopy and Western blotting. Finally he checked the ability of mutants to modulate expression of the inflammatory chemokine interleukin-8 in an epithelial cell line.

They defined seven specific sites of modification, scattered throughout multiple domains of the protein. In all but one instance, lysine->arginine mutations increased the amount of total CFTR protein and, importantly, the amount of fully matured protein. Addition of ubiquitin to different CFTR domains targeted the protein to different pathways for destruction. Modification of the N-terminal and nucleotide-binding domains targeted CFTR to the lysosome, whereas modification of the regulatory domain targeted CFTR to the proteasome. Now you might think that more CFTR and more mature CFTR would also mean more CFTR on the cell surface where it’s needed to function. Yet mutants that prevented proteasomal degradation were actually expressed at lower levels than wild-type CFTR  on the cell surface, even though these mutations produced more mature CFTR  inside the cell. 

So Lee saw that CFTR expression was stabilized by introducing mutations that prevented ubiquitination, but he wanted to find out if it functioned properly. Previous studies had shown that CFTR surface expression and activity suppresses basal inflammatory signaling. In cultured epithelial cells, dysfunctional CFTR activates the transcription factor NFΚB, which goes to the nucleus and turns on genes associated with inflammation. Co-expression with functional CFTR counteracts this program. Lee used one of those inflammatory program genes (interleukin-8 or IL-8) to look at the functional outcomes of his CFTR mutations when co-expressed with a completely non-functional CFTR. Mutants expressed on the cell surface at levels approaching wild-type were non-inflammatory. With mutants that failed to localize to the surface, cells still produced

CFTR trafficking & degradation (source)

elevated IL-8. However, lysosomal inhibition increased surface expression of these mutants and decreased IL-8 synthesis. How did that happen? Lysosomes are tightly linked to endocytosis – that is, internalization of things bound to or embedded in the surface membrane. Like many surface receptors, CFTR is rapidly internalized and shuttled back to the surface (recycling) or shipped to the lysosome for degradation. Lysosomal inhibition ultimately piles up and inhibits endocytosis. Lee’s result might suggest that stabilizing CFTR expression alone is insufficient for boosting CFTR activity. Instead drug discovery and development might also need to CFTR internalization and recycling.

The FDA recently approved the first drug that actually treats the molecular cause of cystic fibrosis. However, this drug addresses only one aspect of CFTR dysfunction, its direct activity. Over a thousand mutations have been identified in cystic fibrosis patients, and mutations that alter CFTR stability and localization present more of a challenge for therapeutic targeting and will likely require a combination approaches. One day, researchers might be able to leverage the sites and roles of CFTR ubiquitination to develop a drug to enhance CFTR surface expression. However, Lee’s data are preliminary, and further studies are needed to confirm the mechanisms of ubiquitin regulation of CFTR. The Zeitlin lab also needs to identify small molecule modulators of the process and define the therapeutic benefit and limits of this approach. In the past few decades, the survival age of cystic fibrosis patients has increased dramatically, but there’s still a long way to go.

Policy needs more science. Science needs more funding. Funding needs limited politically motivated restrictions. These are common refrains among the scientific community, but what do we need to do to get there?

On Saturday, the American Physiological Society hosted a session entitled “How to be a science advocate in your own backyard”, and the American Society of Biochemistry and Molecular Biology held a policy session, “How scientists can save the world”. Both societies fielded excellent panels of professionals engaged in science, science outreach, and science policy: for APS, Gina Schatteman (professor emeritus at UIowa, former AAAS policy fellow, and director of iExplore STEM), Tim Leshan (vice president for government relations at Northeastern University), Michele Sukup Jackson (PhD candidate and member of MIT Science Policy Initiative), and William Talman (professor at UIowa and former president of FASEB); for ASBMB, Tania Baker (professor and head of Department of Biology at MIT), Darlene Cavalier (founder of Science Cheerleader and SciStarter), and Craig Mello (professor at UMass Med and Nobel laureate).

I strongly believe that basic science holds the keys to the universe, and we have a responsibility to do important research and explain it to the world.

- Tania Baker

Advocacy can take many forms, from talking to your neighbor to coordinating with the White House Office of Science & Technology Policy. Schatteman divided advocacy into 2 categories: direct – working through official channels to affect policy, talking to your Congress representative; and indirect or “stealth”, being an advocate just by being a scientist and talking to people you know. Talking to your family and neighbors about what you do is a great way to get started. It’s a (mostly) non-threatening venue to practice talking about science to a non-science audience. Plus your family is kind of stuck listening to you but will also be honest about how you’re doing (Baker commented that your family will smack you if you’re doing a bad job ). Next try a science festival; the presentations are short, and you have multiple chances to give it and modify it as necessary. Or maybe teach a science course for non-majors. Baker mentioned that her department is integrating communications into all parts of the science curriculum. Cavalier is leveraging Science Cheerleader and SciStarter to increase interest and investment of the public in science. In other words, opportunities to engage with non-scientists and promote science are all around us.

If we’re not passionate about keeping science going, we probably shouldn’t be doing it anyway.

- Bill Talman

However, direct advocacy – engaging with legislators – remains critical. Leshan put it nicely: “If you don’t advocate for what you care about, a million other people will be advocating for what they care about, and you will not be heard.” Talman encouraged scientists to not be “the typical NPR listener – all listen and no pay”. In science, we should pay our dues for the opportunity to do science by advocating for science. But approaching a Congressional representative might be an intimidating prospect for many scientists. Starting with local, “stealth” advocacy allows us to become comfortable discussing our science, but we must take a different approach to legislative advocacy. A few key points emerged:

• Do your homework. Find out the representative’s record and stance on issues.
• Hone your message. Have one or two key points.
• Have a clear pitch. Your goal should be to inform legislators of your research and its importance, but there needs to be a clear ‘ask’.
• Make evident how the issue affects the representative’s constituency and how you can help him or her with that issue. Talman recommended writing your areas of expertise on the back of your business card, so that staffers know with which issues you can help.
• Learn how to present your message in a way that others will listen to it – especially when dealing with controversial topics. Schatteman provided herself, a stem cell biologist, as an example.  If she’s talking to someone she knows is a proponent for stem cell research, her approach is straightforward, easy; she can say “stem cell biologist” and know that she hasn’t shut down the discussion immediately. If someone has a record of voting against embryonic stem cell work, she emphasizes “adult stem cells”. Some people may immediate shut down at the mention of “stem cells”, so she starts with a target disease and implications.

If we based [science] policy on science, the world would be a different place. We base policy on emotions and politics.

- Gina Schatteman

• Be flexible. Leshan shared an experience of a meeting in which the representative requested that the scientist end the meeting with a prayer. The scientists obliged and has maintained a strong connection with the representative.
• Follow up and use multimedia to your advantage. For example, make sure that you have a webpage that includes a summary of your research and public engagement in terms that a non-scientist can understand.
• Work with allies such as your institution’s government relations office or your professional society’s policy committee to coordinate efforts.
• If you’re interested and willing, learn the ropes from the inside. Schatteman started off with her university conflict of interest committee; she progressed to first to the university’s and then to a professional society’s legislative affairs committee before spending a year as a AAAS policy fellow – this after she had established here independent research career.
• Legislative advocacy cycles back to the public. The public – our our families, friends, and neighbors – help decide science policy by voting! Mello made the point that as long as the public doesn’t understand or even really care about science, “Congressional representation [of science] will be deficient”. We have to make the benefits of science clear.

If science is to continue to thrive, someone needs to advocate for it – and scientists must advocate for it. We don’t all need to be sitting in meetings on Capitol Hill. We don’t need to do all the advocacy. But we can each make a contribution to keep science and science policy moving forward

Further thoughts

Storify from APS Session

Storify from ASBMB Session

Sunny, a little cool, a bit breezy, but on the whole, not bad for spring in Boston. A fantastic day for a run.

I worked from home a bit before heading to the lab. A couple of hours after lunch, as is my typical routine, I headed to the gym. After about 45 minutes of strength training, I took off out the door, following one of my short loops to tack a couple of miles onto my workout. I passed people with their yellow bags and blue jackets, reminding me that it was Marathon Monday.

For my first four years in the city, I lived only a couple of blocks from a section of the route, and Paramed and I would walk up, watch with inspiration as the wheelchair division zipped by and with awe as the elite runner zoomed past. We’d meander down the last few miles of the course, cheering on runners and feeding on the energy and excitement of the crowd. Last summer, we moved into one of the more distant suburbs of Boston. I had briefly considered trekking downtown to spectate, but I had things to do, and there simply hadn’t seemed to be enough time of late.

I returned to the lab from my own, much shorter run. I grabbed a yogurt from the fridge. My boss wanted to talk briefly about a collaboration. We chatted briefly about another thing, I giving him a good-natured ribbing. I returned to my desk.

As I sat down, my phone vibrated with a text message vibration. Immediately it buzzed again. And then again. Messages from 3 different people, asking if I was in Boston, wanting to know if I was OK.

My stomach knotted. “I don’t know what’s going on, but something’s happened,” I commented to my labmate. I fired off one reply and started logging into my computer to find out what was going on.

My phone started vibrating again, a call this time from Paramed. When I picked up, I didn’t bother with pleasantries. “What is going on?”

“Where are you at? Are you OK?” he asked urgently.

“I’m at work. I just got back to my desk and had 3 different people asking if I was OK. What happened?” I asked.

As I asked, my labmate – having just gotten a text from her husband – answered. “Oh my god. There’s been some sort of explosion at the marathon.”

I thought I’d been punched in the gut. “Oh my god.”

At the same time, Paramed replied. “I wanted to be sure you were OK. There were two explosions at the marathon near the finish. I’m in class. We just heard about it.”

We exchanged a few more words. “I’m glad you’re OK. Please be careful,” he said before we hung up.

Stunned, I quickly began replying to the direct messages queueing up on Twitter, while pulling up the local newsfeed and checking Twitter. I fired off a text to my dad, knowing that my family would be hearing about this any minute. I assured my friends on Twitter that I was far from danger.

Then I called our other labmate. She’s a runner, a crazy runner, the kind who loves pushing through 26.2 miles and beyond. She had qualified and registered for Boston. But she’s also a new mom, and the time away from her daughter to train for a marathon was more than she was willing to give up, at the moment. So she’d decided not to run. But we had no idea where she was, whether she and her husband and adorable 5-month old daughter were somewhere along the course to watch.

The phone rang a few times, and she answered. “Belle, how could…?” Her voice cracked. She knew.

“Are you alright?”

Her voice steadied. “Yes. We were watching at Coolidge Corner [24 mi marker]. We’re almost home now.”

“Good,” I replied. “We weren’t sure if you were watching or where.”

“I just…” She took a breath. “First, who the fuck would do something like this? But second… if I had run, that’s about the time I would have been finishing. That’s my pace – 4 hours, starting at 10 o’clock.”

“I know.” I did know, and I didn’t know what else to say.

“My sister’s best friend is running, and she would have been in the same group. I hope she’s OK,” she continued. [Later she learned that the friend was fine; she'd finished 10 minutes before the blasts.]

“I hope she’s OK,” I replied. “I’m going to get off, free up a ‘line’. I’m sure everyone’s trying to get through, but I wanted to make sure you were fine.”

“Thanks,” she said. “This just hits close to home. I’m hugging my daughter tight right now.”

Then I returned to the coverage. I watched and listened, my brain numb. By the time I tuned in, the anchors were still being cautious, indicating that there was no information as to whether it was intentional or not. But watching the video, I knew in my gut it was. Some part of my brain tried to come up with an alternative but was quickly shut down. Later they reported that, asked whether the blasts were bombs, a law enforcement official responded, “Hell yes. What else could they be?” As the coverage continued, it became evident no one thought this was accident. It was also clear, unsurprisingly, this story was personal. One anchor commented, “I’m infuriated. I hope they get this SOB in a hurry.” In the confused tumble of emotion, this stuck with me.

And yet through all this, the sun kept shining. It didn’t seem right. No, that wasn’t it. It didn’t seem real. It seemed like something out of a movie. Where was the dimming of the light to set the mood?

After the Boston PD press conference, I packed up to head home, wondering how long it would take me. The bus ride was strangely silent, no one daring to speak a word. Terrible things happen all the time – a bombing, a shooting, a fire – but somehow it seemed more acute, because it happened in our city. More than that on a day that we celebrate human commitment, motivation, discipline, achievement, and joy in what is normally a very solitary activity.

We all disembarked at the train station, murmuring farewells to the driver. At the entrance to the train station, I discovered a full security check – bag searches and metal detectors. And yet, despite the hundred or so people waiting to get to their trains, there wasn’t a word of dissent or complaint or protests of missing a train. As the train pulled out of the station, I watched a helicopter hover over the city. It should have been there for the finale of a marathon; knowing it was there covering the aftermath of an attack was chilling.

I now sit at home, sipping a beer and processing this day. The seemingly overwhelming problems of yesterday seem rather small. The worries I had have been temporarily displaced by shock and staggering sadness. There is no sense to be made of this. It was a horrific act. It’s the sort of thing we want to believe is inconceivable – and yet we know from recent history it is not. Innocent people have been killed, and many, many others injured. It took only a few moments on a Monday afternoon to completely change how we viewed the world. Suddenly every neglected bag, opaque water bottle, or abandoned box had become a threat. But even as objects were eyed with suspicion, there was also a great outpouring of aid and compassion for people.

This city and this event are irrevocably changed…

Changed… but not defeated. There’s far too much spunk in this city for that.

via Facebook

]]> http://biochembelle.wordpress.com/2013/04/15/decompression/feed/ 3 biochembelle IMG464 644490_10151402092011958_743569778_n http://biochembelle.wordpress.com/2013/04/08/coming-soon-to-beantown/ http://biochembelle.wordpress.com/2013/04/08/coming-soon-to-beantown/#comments Mon, 08 Apr 2013 11:28:39 +0000 biochembelle https://biochembelle.wordpress.com/?p=1546 Continue reading →]]> If you’re in the Boston area, check out these upcoming events.

Monday, April 15, is the dreaded tax day. But on the bright side, it’s also the date for the next SciO Beantown gathering. The first was a casual & fun affair. This one promises to be equally so, but with a dash of discussion about open access publishing.

A week & a half away is Experimental Biology 2013! Tons of great science, career development, and outreach talks are on the docket. If you can’t make it to the meeting, follow #EB2013 on Twitter. I’ll also be posting from EB2013 as one of this year’s ASBMB meeting bloggers. Expect lots of protein stuff from me. Have a poster I absolutely must see? Let me know

But you do it anyway. You cling to the hope that your experience will be different. Maybe you tell yourself you have something special or that you’ll work harder or smarter. You’ll do the “right” things, or maybe you’ll just get lucky. You’ll find obstacles in your path, but you’ll find a way around or over or through them. Somehow you will make it work. You have to believe that you will succeed. If you didn’t believe that, would you try? Would you stand a chance?

So you do it. You go all in. There are good days that buoy your confidence. There are bad days that test your resolve, but you find a way through them. Most of the days fall somewhere in between, just doing the day-to-day work to keep it all afloat, often without actively thinking about long game.

Then it happens. That fragile dream falls, hits the ground, and breaks into a thousand million pieces. And you feel like you shattered along with it.

While you’re picking up the shards, trying to figure out what to do with what remains and how to move forward, you inevitably find yourself thinking about how you got here. What did you do wrong? What should you have done differently? Should you have put in more or taken a step back? Were you blinded by pride – or naivete? If you’d been a touch more cynical, maybe you’d have been better prepared. Possibly the crash was inevitable, but if you’d held something back, maybe it wouldn’t have hurt so damn much.

That might be the hardest part about broken dreams: They can make you question everything – who and what you are, all you do and how you do it. It can be especially hard when you try to be self-sufficient, when you compartmentalize your life in an effort to keep one part from bleeding into the other, when you’re accustomed to putting forward an air of calm and control even when you’re a wreck inside. The people around you think you’re OK. You’re the strong one; you’re always OK. You say little, so they say little. When they do say something, it’s what they think you need or want to hear – more visions for the future, assurances that you’ll find something new/different/lasting, promises of the wonderful things that will come in time.

What you really need to hear is that you’ll simply make it through the here and now. That you’ll survive picking up the pieces, even though each one cuts deeply as you grab hold. That you’re not alone. That no matter how broken you feel, you’re still relevant, you’re still worth something to someone. Some days you know all of that, without question. Some days take a little more convincing, and you have to tell yourself that you really can do this, that the pain and doubt won’t last forever.

But some days you need a little help. You need to hear someone else say all those things that you know deep down. The thing is, people – even those who are very close – don’t necessarily think to tell you those things because they should be obvious. So you have to reach out and ask for help, which can be harder than it sounds. It means letting go of the pride or logic or whatever it is that’s holding you back. To keep from losing yourself entirely, you have to let some of the cracks show. You have to bare your weakness. The very thing you fear will crush you is exactly the thing you must do. Finding the strength to do that helps you realize you have the strength and support you need not just to survive but to keep playing against the odds.

Many things factor into the decision, but have you stopped to check whether gender might be one?

Last fall, a striking study was published in PNAS using this very scenario. Tenure-track faculty from chemistry, physics, and biology departments at six large research universities were asked to assess the likelihood of hiring a student for a lab manager position. Some saw materials for a male candidate, some for a female one. They were actually the same materials, only with “Jennifer” switched for “John” and “she” for “he”. You might know what’s coming…

John ranked higher than Jen. Actually the faculty “liked” Jen more, but John’s ratings for competence and hireability were higher. John was offered a higher starting salary (by about 15%). And John was offered more mentoring – as defined by providing help with a tough concept or encouraging him to stay in the field or focus on research. The scores for both John and Jen were moderate, but John’s scores were consistently and statistically significantly different.

The study also compared the scores given by male and female faculty. Depending upon your perspective, the result might be surprising or not (I’m in the “not” category). Both male and female faculty exhibited gender bias.

Jo Handelsman, the senior author on the PNAS paper, is a professor of Molecular, Cellular, and Developmental Biology at Yale and an HHMI investigator; the study was run by Corinne Moss-Racusin, a psychology postdoc at the university. At a panel on gender bias in academia this week, I listened to Dr. Handelsman explain how she ended up on a social science experiment. The curious thing about this study is that, unfortunately, the results should not be that surprising. They recapitulate observations from decades of social science studies. With equal qualifications, men are considered more competent, better qualified, worth more money.

Yet as she discussed the issue of gender bias with her colleagues, she kept encountering denial. I’ve heard some of them myself. “Do you really think that’s still a problem?” “It might happen at _____ but not here.” ”That doesn’t happen in science, because we’re trained to look at evidence.” Now we have the evidence that it really does happen in science. So what do we do about it?

From ASBMB Women in Academe Task Force Report (ASBMB Today, Feb 2012)

Often discussions regarding the gender gap in science (with regard to recruitment, advancement, and pay) seem to focus on what women can do (Act this way! Negotiate!) and what can be done to convince us to join and remain in the pipeline (Programs! Education!). In biochemistry, women are joining the pipeline in equal numbers as men. But in academia, attrition occurs at the application phase. Women make up less than 30% of the applicants and appointees to tenure-track positions. Women cite family and work-life balance as influential factors in making career decisions.* These are important issues, and I think the emergence of more family/life-friendly policies are fantastic and beneficial for both men and women.

But we also need to consider what to do about subtle gender bias, which influences the mentoring women receive (or don’t) and the valuation of our work. There were some suggestions in the panel discussion aimed at addressing gender bias more directly – and there’s substantial overlap with tactics to combat racial bias, as well. One was helping both faculty and trainees understand bias and the evidence for it, because raising awareness of bias can reduce its impact. To this end, UW-Madison developed a guidebook for search committee chairs to help reduce the impact of bias and improve diversity in faculty searches. Even games can help raise awareness of bias. Another possibility (which is highly debated in science) was blinding reviews of papers and grants. One of the more subtle ideas was making sure that images of women and minorities in science are visible everyday, because visual priming also reduces bias but only lasts 24 hours.

Much of the conscious bias toward women in science (and society, in general) has dissipated. But the data illustrate that we’ve still got a long way to go. The first step is to recognize and accept that. The next…? That will depend on departments and administrations – with some continual prodding. Looking around my institution, I have hope that the gender gap in science will continue to shrink in the years to come.

* Men more frequently cite “departmental culture” as a major factor. I can’t kind of wonder if things like work-life balance and family issues are coded in it.

Related

Eva Asmen has posted two ideas to fix gender balance that don’t make her cringe

And Nature has a entire feature about the women in science, including an interactive way to explore the NSF data for their biennial report Women, Minorities, and Persons with Disabilities in Science and Engineering.

Element I – Exposure

As a grad student, I was perilously naive about the state of Ph.D. production and career tracks. As far as I knew, research was the primary way of life for one with a science Ph.D., and the other major option was teaching. I might hear about other career tracks about once a year, during a career development session at a conference. I seriously doubt that I was alone in my limited view of science careers. Early in my postdoc years, when I waded into the online science community, I discovered many scientists whose paths had taken them out of academia and/or research, and I realized that life off the tenure track was the norm, not the exception.

Students should be learning about career paths and job market trends early in training. It should be part of their introduction to grad school. Josh Drew is a faculty member in the Department of Ecology, Evolution and Environmental Biology at Columbia University and director of Columbia’s MA in Conservation Biology program. All first year students are required to take a thesis development seminar. Last semester, Dr. Drew covered a wide range of topics: committee selection, research resources, grant writing, and ethics (you can find some of his lecture slides on FigShare). He also thought it important to, per his syllabus for the course, “explore the realities of funding and the post-graduation job market”. He included a lecture on the job market and used social media to invite outside perspectives on science careers.

An intro seminar could easily be done in a single lecture of 60 to 90 minutes a week for one semester. From day one, be honest about the job market. Show the relevant statistics for your field. Use the data available! Professional societies (like American Chemical Society) and funding agencies (see NIH and NSF) have Ph.D. completion and employment data. If your own department has complete data for graduates, put it out there. The point is not to scare new students but to say, “Here is the lay of the land.” Now you get to tell them about the exciting opportunities outside the tenure track or industry research. Bring in 2 or 3 locals and alumni to talk about their careers for a few meetings. In a month, you can cover a lot of possibilities.

Element II – Planning

In terms of career advising in academia, it seems the default assumption is that trainees plan to pursue research careers, and that assumption is often not challenged until late in the game – like around the time you start discussing dissertation writing and defense dates. Although not often fully utilized, completing an individual development plan early during the Ph.D. (say in the second or third year) and revisiting it annually is one way to initiate the discussion of career plans with mentors.

For an IDP to be effective, though, departments and mentors must create an environment where trainees can be honest about their career goals. Too often students and postdocs feel that any path outside tenure track is mocked and disdained, and the truth is, many reactions and behaviors, both subtle and direct, that reinforce this impression. Mentors should be ready and willing to discuss the pros and cons of career tracks but need to remove themselves from the equation. Statements like “I don’t really think you’d be happy doing…” or “I’m not sure that’s what you really want to do…” can shut down discussion pretty quickly.

We also need to be open to talking about alternatives, by which I mean an alternative to whatever your primary career goal may be. Plan A is necessary but not sufficient. The training process in science is long – 4 to 8 years for a Ph.D. then maybe another 2 to 6+ years as a postdoc… We can easily hit a decade of training between completing our undergrad education and beginning a job search. Oh how things can change in a decade – the economy, the market, the funding climate, and the life we have outside the lab. The job we thought we wanted might not be there. Or it might be beyond our reach. Or it may simply not be the job we want anymore. Things change, that’s all. But when things change, we need another plan. We should start thinking about Plan B and Plan C and Plan Q now. We should be able to talk about those plans with colleagues, advisers, and mentors without having our commitment to Plan A questioned.

Of course, the careers for which we’re planning can very quickly expand beyond the experience of our mentors. Most people engaged in training scientists have held one or maybe two types of career positions, i.e. most academics have been academics most of their careers. There’s nothing wrong with that, but they’re not going to be the best source of advice for other careers. Guess what, mentors? It’s OK to admit that. It’s simply one reason why we need Element III.

Element III – Network

If you’ve been in science for a few years, you’ve probably been beaten over the head about the importance of networking. Networking can be a difficult thing, though, especially if you’re like me and find it difficult to walk up and talk to complete strangers or worry about whether you’re annoying someone with that email or wonder how you’re supposed to maintain connections when you don’t have a specific reason for contacting them at the moment. Another challenge is that networks can be very insular. As you’re training at an academic institution, it’s likely that most of your connections will be within the academic research community. How we can we enhance the breadth and career diversity of our networks?

In some ways, it’s easier now than it was a decade ago because of the vibrant online science community. Via blogging and Twitter, I’ve connected with new and established faculty members, editors for society publications, policy fellows, and science communicators. I would never have interacted with people in some of these positions if I’d had to rely on face-to-face introductions.

At the same time, it’s valuable to have more direct connections through institutions, departments, and mentors. You’re the coordinator for a graduate program. About 15% of your graduates have tenure track positions, and I’d wager you have a pretty good idea where they’re at. What about the 25% who are doing research outside of academia? What about the 25+% who have careers outside of research? Programs could potentially help trainees with career planning and development by building an alumni network to tap into. Plus there’s the benefit of data and potential speakers in Element I.

Element IV – Opportunity

As trainees, we need to remember that we have the largest stake and investment in our careers, and ultimately, our career is our responsibility. With the aid of mentors and advisers, we should identify courses and activities that will benefit our career goals. Activities could include writing courses, pedagogy workshops, guest lectures for an undergrad course, outreach activities for an elementary school class, mentoring high school students, grantsmanship workshops, writing for a department blog or a journal spotlight, or courses on law and science. For career development, there is no one-size-fits-all. We have to tailor a plan to our interests and plans. We have to figure out what matters for our career and how to strengthen weak points and improve our strengths.

Even though we must take responsibility for our careers, we still need support from our mentors and institutions. When engaged in activities outside of the lab, scientists – and especially those in training – are often confronted with the attitude of “Why are you wasting your time on __________ when you could be doing things that matter?”, and what’s implied by “things that matter” is research or writing papers or grants. Research and papers are imperative for Ph.D.s and postdoc training. They’re necessary to keep labs funded. Honestly most of us wouldn’t stick around if we weren’t engaged by the research. But papers are not the only things that matter for our careers, especially if we’re considering careers outside of research.

There are tons of career development, education, and outreach activities in our institutions, local communities, professional societies, and beyond. The opportunities are there, but sometimes we hesitate to take advantage of them because of implicit and/or explicit pushback from advisers and administrators. In other words, sometimes we feel like we need permission to participate in these activities, regardless of whether it takes an hour a week or 3 hours once a month or whatever the time commitment might be. Programs might help trainees carve out that time by recommending certain number of hours for “career development activities” per year. Maybe one day, the value of such activities will be widely accepted, but until then, I think it might take some extra encouragement.

Closing Notes

Regardless of what career we pursue, whether it be research or science policy or teaching, our successes will reflect back on the places where we trained. The point of the Ph.D. is to train us as scientists, a very broad goal, but I think programs and advisers should be invested in the career training of their students and postdocs. I don’t think that it will take a complete reinvention of training programs, but rather a few tweaks and additions to existing initiatives to change Ph.D. training into career training and to leave trainees feeling a little more prepared for that great, big, exciting world of science careers.

We talk about how Ph.D. programs and postdoctoral positions are “training phases”, preparing us for… science… and stuff. But for what exactly are these programs training us?

Some will say that Ph.D. and postdoc training are designed to prepare you to be a career in science and, more specifically, a career as principal investigator. If that’s the case, and given that 80% of Ph.D. recipients will not be on that career path 10 years after earning their degrees (see pg. 25 of NIH Biomedical Workforce Working Group Report), then programs are missing the mark by failing to train the vast majority of their wards for jobs they actually choose pursue.

But frankly, I don’t think the point of science training is, or really has ever been, to create a bunch of head lab honchos. The point is to train people to do science. That’s it. A Ph.D. program is meant to lay the foundation for a field of study, to teach concepts and theories, to develop critical thinking and analytical skills. When you finish a Ph.D., you should be able to form a hypothesis, design an experiment, analyze the data, and communicate the results to peers. Actually, I think NIGMS has a pretty good vision in its Strategic Plan for Biomedical and Behavioral Research Training, which outlines:

“… after training, well-prepared students:

• are curious, intelligent and creative;
• are critical, rational thinkers, capable of organizing and analyzing data;
• have a deep knowledge in a specific field but are conversant in related fields;
• are able to formulate significant, testable scientific questions and are technically proficient;
• have the capacity to listen effectively as well as to write and speak cogently;
• are tolerant of ambiguity and resilient in the face of setbacks;
• are able to work effectively with people who have different perspectives, priorities or intellectual approaches; and
• know and follow the standards, responsibilities and culture of the scientific community.”

That’s what you should get out of a Ph.D., and those are the training goals funding agencies should be concerned about. These elements are useful and important for any career track. Yet they’re not specific to any one career track.

So we say we need to do more to prepare young scientists for careers, especially for careers outside of academia. But what exactly do we need to do? How do you introduce additional training without detracting from the primary goals of a Ph.D.? How do you provide the variety of training required to cover myriad career paths? Or another way, how do you give someone skills s/he will need without burdening hir with unnecessary or irrelevant training? How do we move from crucial but rather soft training goals to preparing for actual careers? And what roles should each member – programs, PIs, trainees, funding agencies – play?

Tomorrow I’ll post a scheme floating in my brain, but in the meantime, leave your thoughts in the comments.

By the way, if you’re a grad student and think you have a good idea with “potential to improve STEM graduate education and professional development”, check out the National Science Foundation Graduate Education Challenge. You could pick up a cash prize for a 1000 words.

Science is an intrinsically human endeavor. It takes human curiosity to ask the questions, human logic to design the experiments, human ingenuity to incorporate the results into an evolving model. Despite tropes portraying science as a purely logical enterprise executed by cold automatons, it is wonderfully, woefully, beautifully, messily human.

Yet sometimes it feels as though we’re expected to be both more and less than human. More in that we need to work longer hours at higher efficiency, through health and illness. More research, more papers, more grants – sleep is for the weak! Less in that we should not allow little things like stress and emotions and events outside the lab to influence our pace and focus. Chop, chop, no time for distractions – science waits for no human!

Sometimes the pressure to be more and less than human comes from external sources – those above us in rank or, more often in my experience, those at our own level. But much of the pressure to perform is internal. We see funding woes and dire job prospects and competitors’ papers, or maybe we just see an unanswered question, one that we know we can resolve if only we work hard enough. We dial up the pressure to be “better”. That compulsion drives us and can be a constructive force. We also use it to build unreasonable expectations we set for ourselves.

Sometimes we try to keep our lives outside the lab compartmentalized, to keep it from interfering with our work. But you know how we’re fond of saying that science isn’t 9-to-5? Well, life isn’t 5-to-9. It isn’t so easily contained, packed into a box and placed onto a shelf, to be taken down at a less disruptive time. We must take care of ourselves and the lives we have – lives that bring change and crises and good fortunes that demand our time, focus, and attention.

There are times in life we need to let up on the pressure we place on ourselves. If we’re really lucky (or choose very wisely), then we surround ourselves with people who help us accomplish that. We circulate the stories of the departments and supervisors who set forth maniacal models of how science should be done. We perpetuate illusions of the excessive standards of Real Hardcore Scientists(TM). Do these people and places really exist? Sure. But there are also real scientists doing good work who believe it’s important to have a full life, who do not expect themselves or anyone else to place elements of their lives in suspended animation for the sake of science.

Science demands that we work hard, but our lives demand, on occasion, that we cut ourselves some slack. Science has always been and, unless we are one day converted into cyborgs, shall ever remain a human endeavor, complete with all its humany wumany madness. And in spite of this (or perhaps with its aid), science has marched forward and shall continue to do so with mere humans making the way.

Lately I’ve been dealing with some major stress of the unbloggable kind; such is life. Of course, as fate/luck/coincidence would have it, this comes at a time when I have more than the usual amount of stuff on my plate at work, stuff that requires focus and attention, which can prove difficult when distracted and stressed out. I’ve been through enough stressful occurrences to know that I can easily fall into cycle of letting stress squeeze out those things which make it easier for me to deal with the stress (kind of ironic, isn’t it?).

So, especially since returning from the holiday break, I’m trying to be particularly vigilant in staying out of that cycle. I’m keeping up my food journal and sticking pretty closely to a meal plan. Almost every meal for the week comes from my kitchen, and on the occasion that I do get takeout, I’m mindful of my selections. (That being said, sometimes you need a cheat meal, and last night’s BBQ chicken pizza was heavenly, even if it did come from the freezer section at the grocery store.) I’m limiting my alcohol intake. I’m trying to keep a consistent sleep and work schedule, making an effort to catch the same early train even when I really don’t want to drag my ass out of bed (which can be difficult when it’s 3 friggin’ degrees Fahrenheit outside). I’m also trying to maintain a good level of physical activity.

It’s the last one that can be the hardest to keep up, the one that carries an element of guilt, especially when there’s much to do in the lab, because it actually takes time out of the day. Having a gym across the street helps, and I often try to plan my workout time around long incubations for experiments and take less time for lunch. It also helps that my boss considers maintaining non-science domains of one’s life as an essential part of being a productive scientist. Even so the motivation to work up a sweat can wax and wane. Two weeks ago was great but last week, not so much.

Sometimes, though, a little external motivation can serve as an excellent catalyst. Last weekend, Dr. Isis issued a challenge to earn 50 activity points in one week. One activity point is earned for every 80 calories burned… So that’s an extra 4000 calories in 7 days. I decided to take up Isis’s challenge. I typically walk to and from my apartment to the train, but this week I added a walk from the train to work, when I would usually take the bus. I also bypassed the elevator and took the stairs more this week. These activities to get places I was already going amounted to just over 14 APs for the week. Some days I added an extra 10 or 20 minutes of cardio to pick up an extra AP or two. My workouts – ranging from a couple of miles outside to a couple of hours in the gym (the full breakdown collected here) – accumulated almost 40 APs. I ended the week with 54 APs.

Activity points from the week of January 20th

I also ended up with the first consistent week of running I’ve had in ages – 4 days for 11.5 miles. And I pushed myself hard enough to clear some headspace, even if for a short time, and to a point that made it easier to sleep at night.

Today I’ll be taking a day of rest, after 8 straight days of feeling the burn. But tomorrow I’ll be back in the gym, for the sake of body and mind.

Oh, and thanks for the extra nudge this week, Isis!