Scientific American blogger S.E. Gould talks about bacteria and the art of writing

I'm very excited about my guest today: a fellow scientist and science writer, S.E. Gould is one the first writers I started following back when I joined the scientific blogosphere. Her science blog, Lab Rat, is part of the Scientific American Network blogs and discusses molecular biology and the amazing world of bacteria. Even if you tend to be more of a virus person than a bacterium one (haha, geek joke!), you can't help but drop your jaw in awe when you learn that bacterial colonies form fractal patterns, and that there are some special bacteria, called magnetotactic bacteria, that "contain small nanoparticles of magnetic material which allow them to swim along magnetic field lines."

EEG: Thank you, S.E. for being here today! Tell us a bit about yourself, your scientific background, and your current job.

SEG: I'm S.E Gould, and I currently live in the UK with my husband and baby son. I did my degree in biochemistry, although with a strong microbiology slant, at Cambridge university. After graduating I worked in a lab for a bit, then in a library, before realising that I didn't want to do a PhD. Instead I got a job in science communications. I currently work for a research company, writing abstracts, slide-sets, presentations and posters.

EEG: When did you start blogging about science and what inspired you to do so?

SEG: I've always loved writing and at university I used to write constantly, scribbling down story ideas in the margins of lecture notes. I started the blog mainly as an exercise to try and channel my writing into something that would help me pass my degree. My biggest inspiration was definitely Ed Yong of Not Exactly Rocket Science. At university I'd sort of got caught in the mindset that science was incredibly complicated and required lots of lectures and degrees to understand. Ed's blog showed me that it could be explained in a way a lay audience could understand. With each of my posts I try to write so that someone with no science background can get a vague understanding of the main point of the post, and hopefully catch some of the enthusiasm and excitement I feel for the subject. I know I don't always succeed but hopefully I'm improving.

EEG: I'd say you do succeed, S.E., and in fact it's one of the reasons why I enjoy your blog so much. The other one is the amazing creatures you talk about: what motivated you to write about bacteria?

SEG: They were the part of science I was most interested in at university. I love them because they have to do everything that a multicellular organism has to do, except they only have one small cell to do it in. And I love the plasticity of their genome, the fact that they can chop and chance lots of DNA. I had a biochemical background and from the point of view of biochemical processes bacteria are much more fascinating and diverse than eukaryotes.

EEG: What do you love the most about science communication?

SEG: I love that there's so much great science out there to write about. I am unashamedly a science cheerleader; rather than critically analysing papers my blog is about finding interesting research and trying to share it with as many people as possible in a language they can all understand. I love finding the best ways to communicate information - at work I'm always trying to condense tables and paragraphs down into short sentences and diagrams. Although the blog usually contains a lot of writing I think the best way to communicate science is through diagrams, and it's always fun making slide-sets trying to get rid of as many words as possible while still keeping the message coming through.

EEG: That is certainly one of the best skills that science and science writing teach you. On the topic of science blogging, what do you think about using pseudonyms to avoid controversy? Do you think a pseudonym might affect the writer's credibility?

SEG: I completely support the use of pseudonyms. I started using a pseudonym for safety reasons, and even now I prefer to be known by my initials than by name on the internet. A writer using a pseudonym will have less credibility, at least initially, because they can't use their already existing credibility as a scientist. Instead they have to build it up via their blog. By producing well researched and interesting blog posts their credibility will increase, and I think scientists using pseudonyms have the potential to be just as credible and trustworthy as named ones. The only difference is that they have to put a lot more work into getting to and maintaining that state.

EEG: But wait, you write fiction, too: can you tell us a bit more about that? When did you start writing fiction? And where do you find inspiration?

SEG: I've written fiction since I was tiny. When I was younger it was mostly fantasy and science fiction stories, almost all of which I started and never finished! When I started university I got involved in some online fanfiction communities which was a great way to try out different styles of writing and get lots of feedback from a supportive group of people. Once I left university I was looking into getting something published and found the online publisher Less Than Three Press. Because they were an independent online publisher I didn't need an agent or a background of previous publications and everything was carried out by email. The first story I sent them, Chrysalis, required a lot of editing and was quite a steep learning curve for me in terms of understanding what a publisher would expect and how to work with an editor. I've published two more short stories with them since then, and written another for a Dreamspinner Press anthology.

For the foreseeable future I'll be sticking with online publishers and probably keep writing for the niche of LGBT fiction. It's a great genre to write for, and has a decent sized following of readers. I've had a few people ask me why I only write gay romance and the answer is, as a great man once said: because you keep asking me that question.

A full list of my published stories can be found on my fiction blog.

EEG: That is so cool! Congratulations on your published work! And thanks so much, S.E. for this insight into your writing, both fictional and non. I wish you all the best with your work and I look forward to learning more about the world of bacteria.

If you haven't already, don't forget to add The Lab Rat to your RSS feed, you won't regret it. Besides being fascinating little creatures, just like viruses, bacteria are a great source of inspiration for all sorts of science-fiction stories. ;-)

My photography website just got a make-over!

Last December I participated in the monthly Self-Portrait Challenge over on G+, an event organized by the Art of Self-Portraiture Community, led by the amazing photographer Lotus Carroll. Aaaaaand... <drum roll, please> my entry (above) was awarded a one year pro-membership with SmugMug, a hosting site for photographers!

As a result, I have a brand new website, and it's soooo beautiful!

I'd appreciate your feedback on look, feel, etc. Also, as a motivation to try and test the shopping cart (hehe), I have a sale going on right now: spend $20 and get a 25% off discount, just use the coupon code "kickoff14" at check-out -- offer valid until next Wednesday.

So, what are you waiting? Go check it out and tell me what you think! :-)
Should you have problems of any kind while surfing, please do let me know -- the wonderful people over at SmugMug are all in stand-by to help us out.

Thanks so much!

January Moonrise

I sure love full moons out here in New Mexico. :-)

This was after my first real estate shot. Can you imagine the view from that house?

Mitochondria to the rescue

Yes, I confess I'm quite fascinated by mitochondria. Not only their well functioning seems to be correlated to lifespan, like I discussed last time, but it's also implicated in cancer.

Briefly, last post taught us that mitochondria provide energy to the cell by producing ATP through four different oxidative complexes. However, mitochondria's oxidative activity wanes with age. Researchers found one pathway in particular that is activated in low-fat diets and high-exercise regimens, which can reverse the decrease in oxidative activity.

In 1926, a German physician named Otto Warburg discovered that, contrary to healthy cells, which produce ATP through the mitochondria oxidative complexes, cancer cells produce most of their ATP through a process called glycolisis. Glycolisis can be thought of, in lay-man terms, as fermentation of sugar. Thanks to this discover, which was confirmed across many different lines of cancer cells, Warburg was awarded the Nobel Prize in 1931. Warburg hypothesized that the underlying cause of cancer was a dysfunction in the mitochondria that led to upregulation of glycolysis.

If glycolysis is a hallmark of cancer, can it be used to target cancer cells and destroy them, while leaving the healthy cells untouched? Furthermore, can we "cure" cancer cells by restoring the mitochondria oxidative complexes?

The answer to the second question appears to be no: while it is true that mitochondrial activity slows down in cancer cells, this is not always due to mitochondrial dysfunction, rather, to disruption in signaling pathways that regulate glucose uptake and production. As the word suggests, the oxidative complexes in the mitochondria produce ATP using oxygen, whereas glycolysis produces ATP without the use of oxygen. The upregulation of glycolysis could be an adaptation of tumor cells due to their fast proliferation. Healthy cells receive oxygen through blood vessels. However, tumor cells outgrow the production of new vessels and therefore, in order to survive, they have to adapt to the absence of oxygen. Normally the absence of oxygen would lead to cell death, which is regulated by the p53 protein. As it turns out, p53 is either mutated or downregulated in tumor cells.

So, what does the Cell paper on aging teach us about cancer?

Remember that when it comes to cells, there's never an on/off switch, but rather a cascade of signals, i.e. chemicals that activate one another sort of like in a domino effect--what we call a "pathway." To reconstruct a pathway you have to look at each domino piece and how they interact with one another. That's why things get a bit complicated.

The upregulation of glycoysis happens through a protein called hypoxia-inducible factor-1, or HIF-1alpha. HIF-1alpha is a transcription factor, in other words, a protein that binds to DNA and regulates the expression of certain genes. Gomes et al. [1] found that HIF-1alpha induces some kind of metabolic reprogramming, not just in cancer cells, but also in normal tissue as a consequence of aging. Previous studies have shown that a high-fat diet increases levels of HIF-1alpha in the liver.

In [1], Gomes et al. induced a decline of mitochondrial activity in mice by knocking out the SIRT1 gene, a gene that codes for a protein called Sirtuin 1. It turns out, without SIRT1, not only did the researchers see the decline in mitochondrially encoded oxidative complexes, but they also observed high levels of HIF-1alpha and high expression levels of the genes targeted by HIF-1alpha. Gomes et al. restored expression of SIRT1 using a molecule called NAD+, thus restoring mitochondrial activity and lowering again the levels of HIF-1alpha. It would be interesting to see if this molecule could be used in cancerous cells as well, and if downregulating glycolysis would eventually kill the cancer cell given that they have to grow in a low-oxygen environment.

[1] Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, & Sinclair DA (2013). Declining NAD(+) Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging. Cell, 155 (7), 1624-38 PMID: 24360282

The secret to a long life? Active mitochondria!

For quite a while now we've known that if we want to live a long, healthy life, we must exercise regularly and be good about what we eat. Recent studies have added another piece to the equation: maintain mitochondrial function.

Mitochondria are organelles found in every cell of our body. They hold a very important function: they provide energy to the cell. Most cellular processes take place using energy stored in a molecule called adenosine triphosphate, or ATP, and most of a cell's supply of ATP is produced in the mitochondria through a process called oxidative phosphorylation. Mitochondria are also the only place outside the nucleus where you can find DNA: human mitochondrial DNA (mtDNA) is circular, and it contains 37 genes. Contrary to nuclear DNA, mitochondrial DNA is not unique to every individual because it is inherited from the mother's side only and, therefore, does not undergo parental genetic recombination.

How do mitochondria fit in the longevity puzzle? Lanza et al. [1] found a progressive decline in mitochondrial DNA abundance in skeletal muscle cells with age. The progressive decline of mitochondrial activity in muscular tissue implies less ATP synthesis, and, therefore, less energy for the cell. In addition, mitochondria play a role in regulating programmed cell death, "a vital mechanism to regulate development, cell numbers, and prevent the accumulation perilous tumor cells." Therefore, it is possible that mitochondria influence the loss of muscular mass associated with aging through upregulation of apoptotic processes. In their review, Lanza and Nair [1] cite studies that have shown that mitochondrial activity is reduced in older adults, though it seems to be preserved across similar activity levels, implying that exercise can slow down and even prevent this progressive loss.

"Mitochondrial DNA copy number decreases with age, which could account for the reduction of mitochondrial gene transcripts and therefore, the proteins encoded by these genes [1]."

Even though it's not clear whether the decline in mitochondrial function is a cause or a consequence of the senile phenotype, there have been some new studies suggesting that mitochondria play a major role in regulating cellular aging, and that restoring mitochondrial function can indeed slow down the aging process.

To understand why this is the case, let's go back to mitochondria's main function: they synthesize ATP through oxidative phosphorylation. Most proteins involved in this process are encoded in the nucleus, though 13 are encoded by genes in the mitochondrial DNA. This implies that in order for oxidative phosphorylation to take place and ATP be produced, the nucleus and the mitochondria have to work together and communicate closely. As we age and lose mitochondrial function, this close network weakens, causing loss of oxidative capacity.

Researchers from Harvard Medical School noticed that though there are 4 different oxidative phosphorylation complexes, the one encoded by exclusively nuclear genes does not decline with age, while the others do. Therefore, they hypothesized that the progressive decline of oxidative activity was due to a decline in mitochondrially encoded genes. This study, a joint project between Harvard Medical School, the National Institute on Aging, and the University of New South Wales, Sydney, Australia, was published recently in Cell [2]. In the paper, the authors describe a pathway that regulates mitochondria activity in skeletal muscle cells and show that, by knocking out the pathway in genetically modified mice, they could mimic aging by decreasing mitochondrially encoded oxidative phosphorylation complexes. On the other hand:

"Current dogma is that aging is irreversible. Our data show that 1 week of treatment with a compound that boosts NAD+ levels is sufficient to restore the mitochondrial homeostasis and key biochemical markers of muscle health in a 22-month-old mouse to levels similar to a 6-month-old mouse [2]."

The NAD+ compound the Harvard researchers talk about in their paper is a coenzyme that restores communication between the nucleus and the mitochondria. When levels of mitochondrially encoded mRNA are restored, ensuring that the production of mitochondrial proteins participating in the oxidative phosphorylation complexes is no longer declining, the pathways associated with low-fat diets and high exercise regimens are once again activated.

"All of the main players in the nuclear NAD+-SIRT1-HIF-1a-OXPHOS [oxidative phosphorylation] pathway are present in lower eukaryotes, indicating that the pathway evolved early in life’s history. This pathway may have evolved to coordinate nuclear-mitochondrial synchrony in response to changes in energy supplies and oxygen levels, and its decline may be a conserved cause of aging [2]."

Even more remarkable is that the pathway the researchers found is implicated in cancer tissues, too. So, while it's worth reminding ourselves that aging is NOT a disease (I hate it when I see commercials that tell me they found a "cure" for wrinkles!), there are many age-related diseases, including cancer, that could benefit from these findings. As always, it remains to be seen whether the mouse model is reproducible in higher mammals, but finding and understanding these pathways is indeed a great step forward.

[1] Lanza IR, & Nair KS (2010). Mitochondrial function as a determinant of life span. Pflugers Archiv : European journal of physiology, 459 (2), 277-89 PMID: 19756719

[2] Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, & Sinclair DA (2013). Declining NAD(+) Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging. Cell, 155 (7), 1624-38 PMID: 24360282

My challenging, humbling day job

This morning, when the alarm clock went off, I yawned and groaned and wished I could stay in bed all day. And then I thought of all the people who don't have a job and don't get a pay check, so I kicked my ass out of bed and went to work.

Don't get me wrong, I love my job. But I don't kid myself: scientific research is rewarding 1% of the time and hard and frustrating 99% of the time. In school you are given ideal datasets tailored to the statistics you learn in class. In real life datasets are very much imperfect: experiments don't always go as planned, they don't always get fully funded, and you end up with a small sample size or a poor study design. Textbook stats no longer apply. You have to come up with new strategies.

My job is challenging. My job is humbling. Every day I am reminded that I'm so not the smartest person on earth, that I'm very much fallible, that I have limitations. Every day I'm reminded of the millions of people that are dying of AIDS. Every day I'm reminded of how lucky my kids are.

It's good to have reminders that keep you in check and make you grateful for what you have.

So there.

Thank you hard, challenging, and humbling job.