A ‘crappy’ PhD: my journey into microbiome research

When people ask me what I do, I usually blurt out a bit of jargon along the lines of “I study the microbiome seeding process in the fetal gut and the immune and metabolic consequences of disruptions to this process”. Most people blink at me and then move on to another topic of conversation. I don’t respond in jargon because I have poor scicomm skills, I do it because, if pressed, I’d have to admit that “I study the microbiome seeding process in the fetal gut” translates to “I spend my days digging through freshly excreted baby poop for bacteria” – which is a fairly unglamorous response.

So why on earth have I chosen such an unglamorous PhD? My background is in obstetric (pregnancy) research, and after my masters I decided to take a year off to travel. Before I left for my year abroad, I was lucky enough to catch a presentation by Kjersti Aagaard (a leading microbiome/pregnancy researcher) on the human microbiome.

A microbiome is a community of micro-organisms (bacteria, archaea, viruses, fungi, protozoa), the space they inhabit, and they conditions surrounding them. Essentially it’s a micro-ecosystem – a teeny tiny universe in itself. When we talk about the human microbiome we are referring to the teeny tiny universe of microbes that exist on and in our bodies. Most of these microbes inhabit our guts, where they play an enormous role in our health. Until recently, the sheer number of microbes and their importance in the functioning of our bodies has been overlooked. But the development of better and more affordable metagenomic technologies (that is, technology for sequencing DNA, which allows us to precisely identify different species of bacteria) has ushered in the “microbiome revolution” throughout the past decade. Increasingly we’re recognising the vital role our gut microbiomes play in our health and the way in which modern lifestyles can disrupt the finely tuned relationship we have built with our resident microbes over the millennia. Importantly, our gut microbiota protect us from invading pathogens, produce key nutrients, control our metabolism, influence our behaviour, and calibrate our immune system.

The “microbiome revolution” has seen a rapid spike in microbiome related research following a leap forward in metagenomic technology

The “microbiome revolution” has seen a rapid spike in microbiome related research following a leap forward in metagenomic technology. Graph produced by Lisa Stinson.

 

I was enthralled by Kjersti Aagaard’s presentation. Throughout my year of travel, news about the human microbiome kept popping up and grabbing my attention. It seemed that the human microbiome was being pinpointed as a culprit for every imaginable human ailment from obesity to asthma. So when I returned to Perth to begin my PhD, it was obvious to me that I had to study the microbiome. Coming from an obstetric background, my first thought was to study the vaginal microbiome. So I launched myself into writing a literature review and quickly hit a wall. I wanted to include a paragraph about the origins of the vaginal microbiome (when and from where is it acquired?). But no one seemed to be able to answer this question. The prevailing dogma stated that the vaginal microbiome and all other human microbiomes are established at birth when a baby passes through its mother’s vagina. But if this were true, what about Caesarean delivered babies? No one had ever demonstrably proven that babies were sterile until birth and acquired a big dose of microbes as they pass through the birth canal. In fact, there were a handful of studies saying the opposite – that neither the fetus nor the womb was sterile at all. I knew then that I had found my PhD project.

My literature review revealed that not only is the fetus seeded with maternal microbes before birth, but these microbes have a role to play in shaping the fetal immune system and preparing it for life outside the womb. Considering the enormous role our gut microbes play in health and disease, I decided to study the establishment of the fetal gut microbiome. Unfortunately for me, this means a life centred on collecting and analysing baby poo for the next 3 years. The very first poo that a baby does (called ‘meconium’) can act as a proxy for the gut contents of the baby before it was born. Other researchers have already established that meconium is not sterile, so I’ll be adding to this knowledge by comparing the meconium microbiomes of babies from normal healthy pregnancies to those from pregnancies complicated by an infection in the womb (called ‘chorioamnionitis’). I’m hoping to find out if a pathological infection can interrupt the normal microbiome seeding process, and if so, if this would have immune and/or metabolic consequences for the child.

Another day, another nappy

Another day, another nappy…

It’s a daunting task that’s thrown me into the deep end of microbiology and metagenomic technologies (areas which I previously had zero experience in), but I have a supportive and knowledgeable team of supervisors and mentors behind me. And even though I sometimes find myself digging through dirty nappies thinking “why am I doing this to myself?”, deep down I really enjoy it. Ultimately I’m doing this to answer questions that I couldn’t find the answer to anywhere else. My rather unglamorous passion for poop has come from pure scientific curiosity. So my crappy project really isn’t all that crappy after all.

Lisa Stinson

University of Western Australia

@lisafstinson

https://microbiomemusings.wordpress.com/

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News Round-Up January 2016

Hello, and welcome to the #bioscinews round-up! This is the place where you can find all the important biosci new stories from the past week, in a short, digestible paragraph.

The start of the year is always a busy one, with having to settle back into work/studies and coming to terms with the fact that the next major holiday is months and months away (weep), so hence this post will be a whole month’s news round up instead of a weekly news round-up. We shall get back to the weekly news round-ups next week! Until then, enjoy what January had to offer…

This month’s news

The mummified remains of “Ötzi the Iceman” were originally found in the Austrian alps in 1991, but continue to provide fascinating insights into the lives of the Chalcolithic Europeans. These Europeans lived during the Copper Age, the beginning of the Bronze Age, around 3000-5000 years ago. The most recent study to focus on Ötzi has revealed that, at the time of his death, he had a strain of the Helicobacter pylori (H. pylori) bacteria in his stomach. H. pylori is linked to severe inflammation in the digestive system and can lead to certain cancers. However, it does not match the strain which currently tends to inhabit European stomachs. The authors suggest this may reveal new findings concerning human migration patterns at the time and, while the discovery is exciting, caution must be taken when drawing conclusions from a single data point.

sn-iceman

In further human evolution news, there may be links between Neanderthals and our immune systems. Comparisons between human (Homo sapiens) and Neanderthal genomes has suggested that some of our immunological genes came from interbreeding with Neanderthals. These genes – known as the Toll like receptor family – are important for our innate immune system, which initially mounts a defensive response to pathogens. The innate immune system is also largely involved in allergic responses. So, thank our predecessors for our ability to respond to infections rapidly, but you can also silently curse them next time your hay fever acts up!

Neanderthals-diginean3

In some slightly stranger insect-related news, to confirm that praying mantises do see in 3D and to create a system to confirm the same in other insects, scientists from the UK and France have created 3D glasses for insects. The glasses are similar to the red-green plastic system that was commonly used in the 80’s and 90’s for movies, but different colours were used. Since insects’ eyes are sensitive to different wavelengths than human eyes, the authors used green and blue plastic lenses instead of the traditional red and blue. While this is a strange set-up for sure, maybe it will help us learn more about insect vision in the near future! The images are pretty cool to look at too…

Newcastle University research into 3D vision in praying mantises by Dr. Vivek Nityananda. Pic: Mike Urwin. 151015

Newcastle University research into 3D vision in praying mantises by Dr. Vivek Nityananda.
Pic: Mike Urwin. 151015

Explaining the evolutionary origins of life is still an active pursuit by biologists, but we now have more insight into how life became multicellular. In order to become a multicellular organism, some form of organisation is required. For this, cells take advantage of some structures involved in cell division, the mitotic spindles. These are fibres which are involved in separating the chromosomes (or DNA) of cells when they replicate and divide. Recent work has helped to explain how this complex system was adapted into a system to help organise multicellular life. A single mutation seems to be responsible, for co-opting this system of cellular organisation into one for organismal organisation. The article is rather technical, but is an excellent example of evolutionary modifications.

Unravelling multicellularity

Scientists have always been interested in the diversity of lifeforms on Earth, and this month a new interesting puzzle was discovered. Often, the same genetic background can result in many different body forms (called phenotypic plasticity), but this worm puts other phenotypically plastic organisms to shame. It produces five different forms from the same genes! The worms are often found in figs, and now we know they have five different physical forms depending on which species of fig they inhabit.

Five in one

Antibiotic resistance is a problem our news digests have covered before, and this issue continues to concern scientists and medical professionals the world over. Nanoparticles are tiny particles which have been considered for use against bacteria previously, but they have some issues: they are not cell selective. So, if you were to treat a patient with specific nanoparticles that can ‘destroy’ foreign cells, they would also destroy their own cells, which is of course not a good way to treat a bacterial infection. Recent work, however, shows promise in designing more specific nanoparticles to specifically target bacterial cells and leave our own healthy cells undamaged. Hopefully nanoparticles can be added to our arsenal against bacterial infections some time soon!

Nanoparticles help target antibiotic resistant bacteria

We all probably know by now that we are host to many organisms apart from ourselves, from beneficial bacteria, to mites in our eyelashes. But maybe you haven’t given much thought to who you share your house with? Well, these scientists were curious about what might be lurking about the average house. They surveyed 50 different houses in California and found a remarkable diversity of Arthropods (the Phylum which includes insects), with up to 200+ species in a single house! But don’t worry, the most abundant arthropods found were all completely harmless.

You're never really home alone...

At school, we all learned that lizards and other reptiles were cold-blooded, that is, they need to absorb heat from their environment as they do not produce their own bodily heat like humans do. But, I guess we also all learned that, at some point in life, that there is always an exception to every rule. Well, we’ve finally found the exception to the cold-blooded lizards. The Tegu lizard, native to South America, has been found to produce some bodily heat in certain seasons. We don’t know how they do this yet, but it has been suggested that they increase the activity of certain organs, like the heart or the liver, to produce extra heat during the breeding season. The more in depth we study nature, the more strange and fascinating it gets!

Warm Blooded Reptiles

Our final news story for the month is potentially very exciting for age-related blindness. Retinitis Pigmentosa (RP) is a gradual blindness that progresses with age, and current treatments only manage to slow the decline in vision. We know which gene is responsible for this condition, but so far, efforts to restore the function of this gene have not been very successful. Some new work making use of CRISPR gene editing technology may provide some hope however. Previous gene therapy efforts have focused on introducing some separate functional copy of the gene in question, but often this replacement copy degrades over time and the therapeutic effects go with it. With CRISPR, we can take out the defective copy of the gene, and replace it with a functional copy which will last longer and prevent disease progression. However, this work has only been done in rats, and CRISPR technology is currently not approved for therapeutic applications in human tissue. Besides that, CRISPR is also embroiled in a copy-right dispute at the moment, so it may be a while before we know if this can be applied in a clinical setting.

CRISPR may help prevent eye degeneration

 

We hope you enjoyed this month’s news round-up, thanks for reading!

Devon Smith, The University of Sheffield, @devoncaira

Julie Blommaert, The University of Innsbruck, @jblommaert92