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/

Advertisements

Can we make chicken limbs grow?

Most people only view chickens as a source of meat. A means to an end to make a nice, tasty stir fry or a heart-warming soup. However, over the past few years, I have been using them to understand more about the development of the muscles. I am interested in what controls and signals muscle development, essentially: can I grow limbs from basic tissue? If I succeed, such a technique could potentially be used in medicine to help amputees and people who suffer with muscle related diseases. What’s more, it also has potential uses in the food industry.

So why chickens? 

Much scientific research is carried out in models such as mice and rats, however for my research, this is not the case. My work uses chicken embryos. The use of chicken embryos poses fewer problems concerning animal welfare and early chick embryo development is very similar to that of other animals. They are so similar that at early stages it can be very difficult to tell the difference between chicken, human or reptile. Can you tell the difference? I use chicken eggs that are freshly laid and incubated until a certain stage of their growth. Because the embryos are sheltered in an egg, it makes them easy to handle, although if you drop one there is one big omelette on the floor…

Development of Muscles

The official term for muscle development is Myogenesis and it occurs during embryo development. Most of the muscles that form the main body and limbs originate from the mesoderm, one of the several types of tissue that can undergo differentiation. The process of differentiation is when a cell becomes defined to a particular tissue type (e.g. a muscle cell) and it beholds a specific job or function. Think of a student at university: their bachelor’s degree is very broad but is in a defined field, they then go on to do a masters learning about just one specific area. They can then go further, become more ‘defined’, and do a PhD.

Credit: Poultry CRC

Credit: Poultry CRC

During early development the mesoderm forms defined segments called somites. It is from these somites that muscle originates. Normal body (trunk) skeletal muscle forms due to various signals, however, development of the limb muscles uses a completely different set of signals. During limb development, young muscle cells (known as a myoblasts) that express a muscle marker known as Pax 3 move into the limb bud. This movement (or migration) only occurs at specific sites, just like bird migratory events only happen at certain times of the year. Once these young myoblasts have migrated they form two distinct muscle masses: the dorsal and ventral masses. Once these masses have formed, the myoblasts begin to differentiate and express specific markers of differentiated muscle, including Myf5 and MyoD. The muscles of the limb will then continue to grow and develop into the normal defined limbs that everyone recognises.

Why muscle development?

Muscle development provides an excellent model for developmental science. Up until now, research has focused on the regulation and development of somites, and the development of limbs is currently not understood. Nobody understands how limbs grow in such specific locations, therefore I aim to use muscle development in chicken embryos to shed light and understand the processes that regulate differentiation during my PhD project.

 

Helen Anderton

The University of Nottingham

@Helen_Anderton1

Meet our new cousin: Homo naledi

Something very exciting happened this year. We heard the announcement of a new species – quite ancient but closely related to our very own species: the Homo naledi.

In October 2013, two recreational covers (Rick Hunter and Steven Tucher) happened upon some fossil bones within a cave, known as the Dinaledi chamber, located within the Gauteng province of South Africa.

Continue reading