 Moms, you are, what your babies make you. Good evening, everyone. My name is Matt, and I'm doing my PhD in the Department of Statics and Gynecology based in the Faculty of Medical and Health Sciences. First, I'd like to thank Exposure for giving me a chance to present here today and organizing this fantastic event. I'm really grateful to be here, and today my story will be on that, moms, you make us. But did you also know that we make you? Now, I'm gonna begin my slide with the introduction of the chimera. So, in Greek mythology, a chimera is a hybrid creature depicted as a fire-breathing lion with a head of a goat on its back and a snake for its tail. Now, the ancient Greeks, they were definitely onto something because it happens that this isn't just a figment of imagination. It actually happens in real life during pregnancy. Now, we call this chimerism fetal chimerism, i.e. baby chimerism, and it is described here that fetal baby materials pass into the mother's body during pregnancy. What's even more fascinating is that this same fetal materials can be seen detected in the mother decades after or even throughout the lifetime of the mother after giving birth to the baby. Now, although there is no fire-breathing involved, this is really heavily fascinating stuff from a biological and hopefully from an audience point of view because fetal chimerism has been correlated to a diverse list of health effects in mothers. For example, the presence of fetal chimeria in the mother's body has been correlated to protection, such as increase in wound healing, protection against breast cancer, as well as increased protection against Alzheimer's disease. However, it's not always sunshine and rainbows because it has also been correlated to negative effects as well, such as increase in the risk of colon cancer, as well as Parkinson's, just to name a few. Now, these are some serious health implications, and there's actually been a lot of research effort in the past to try and identify and investigate the correlation between fetal chimerism and how these diverse health effects are coming about. However, many parts of it still remain unanswered, and most of it is still shrouded in mystery, until now. So, in my PhD, we try to tackle this mystery by providing an explanation of our own as to how this might be occurring. So, in my PhD, we hypothesize that during pregnancy, the placenta releases vesicles that contain fetal DNA directly into the mother's blood circulation. Here, this then delivers into the mother's cell creating fetal chimerism. Now, to better understand this hypothesis, I'm going to break it down into three parts. First part, I'll be talking about the placenta. Second, the DNA. And then finally, I'll be touching upon the vesicles. So, at the core of my hypothesis involves the organ called the placenta, and here is the depiction of the fetus and the placenta depicted in red inside the mother's womb during pregnancy. Now, the placenta is an organ that develops during pregnancy and it's a transient organ that resides for around eight to nine months in the pregnant mother. Now, the most obvious functions would include delivery of nutrients to the baby, as well as allowing the baby to breathe. Fun fact of the day is that this organ is actually a part of the growing fetus and not the mother. Therefore, it follows that it contains fetal DNA only. So then, what is DNA? Well, we might be more familiar with DNA from hit PV forensic shows like CSI Miami, Bones, or even Jurassic Park. And the common theme in all of these TV hits is that DNA is the blueprint of life, and that each individual contains a unique DNA sequence. So, this is basically what a DNA looks like, a twisted-up letter. And to describe the function of the DNA, I'd like to bring in the book analogy. Using this analogy, each bar of the letter represents a single letter of the alphabet. We call this base pair in biology. By itself, it doesn't mean anything. It doesn't have any function. However, if the DNA is long enough, it'll code for multiple, it'll code for multiple letters of the alphabet that combine to form a comprehensive word. Now, we call this gene. Therefore, it follows that the entire DNA sequence will form the story of the book, i.e., the individual, you. So then, where is DNA located? So, here is a simple depiction of a cell in your body, and DNA should be located in almost every cell in your body. Now, I'm going to bring in another analogy here. I'd like to represent the cell as being a computer, and the human blood circulation as being the Internet. Now, both the cell and the computer, they perform many different functions, one of which is the transfer of information from one computer to another. To do this, they must access the Internet, and they send out something like emails. It is essentially the same in your human body. We, for one cell to communicate with a different cell in different parts of the body, our cells will produce and release what is called vesicles into their surrounding that end up in the blood circulation. So, this brings us to our final part of our hypothesis, vesicles. So, in this analogy, vesicles can be seen as very tiny biological emails. Again, they're very tiny, around 100 to 1000 nanometers in diameter. And in the past, the scientific community has always regarded vesicles as nothing more than rubbish. i.e. junk mail. However, in the last decade or so, a tremendous amount of evidence has emerged showing that these vesicles actually carry quite valuable biological cargo or information in the form of, let's say, an email attachment. And this is what allows for communication between cells into a different part of the body. Now, the placenta is an extraordinary organ. It releases truckloads of these vesicles directly pumping it out into the material mother's bloodstream. And if these vesicles from the placenta did have an email address, it looks something like this, vesicles at placenta.nz. And in my PhD, we are the first to propose that these placental vesicles contain fetal DNA as its biological, I mean, as its email attachment. So, here is a quick cartoon to illustrate how this all happens overall. We begin with a pregnant mother with the fetus depicted here as green. Again, we see that fetus and the placenta depicted here as red. Now, the placenta produces vesicles that contain fetal DNA, like so. And this is then released into the mother's bloodstream. It travels about, and some of these vesicles may make its way to a local mother's cell. Here, they are ethnobody cells with potential transfer of the fetal DNA content carried in these vesicles into the mother's cells DNA, thereby creating fetal chimerism. And depending on the different parts of the fetal DNA that has been transferred, we propose that different outcomes may arise. So, let's say, for example, the transferred fetal DNA depicted here as yellow happens to be a tumour suppressor gene. Then this may lead to reduced risk of cancer in mothers. Let's say that it happened to be a blood vessel formation gene. This will lead to an increase in blood vessel formation, and therefore increase aid in mothers' wound healing. So, this brings us to the first part of my first aim of my project, which was to determine if fetal DNA really was present in my vesicle samples released by the placenta, and if so, in how much quantity. So, here is my method. We begin with a placenta. We put it into an insert system, which allows us to collect the falling vesicles from the overlaying tissue, and then we collect out our solution that now contains these population of vesicles. We then extract the DNA from it. And here is my wealth factor. This data shows that total quantity of fetal DNA carried in vesicles released by the placenta every single day. Now, this data not only shows that fetal DNA is indeed present in these vesicles, but they are present in extreme abundance. In fact, the placenta releases 17 milligrams of foreign fetal DNA pumping it directly into the mother's blood every single day through our pregnancy. Now, is 17 milligrams a large amount of DNA? Well, this is equivalent to the DNA amount of 3 million cells. So, the answer is yes. This is quite a considerable amount of foreign DNA that is continuously circulating about in the mother's circulation and potentially exposing the mother's body cells. So, following on from this, I had one concern. It was that vesicles were quite tiny. So, the question now was, could these fetal DNA carried in these tiny placental vesicles still be long enough to code for functional genes? i.e., could they code for a comprehensive word using the book analogy of the DNA? And this brings us to my second aim, to determine the length of the fetal DNA carried in these placental vesicles. And here is that result. We see that very clearly that placental vesicles are more than capable of holding a DNA size of around 20,000 base pairs. Now, is 20,000 base pairs long enough to code for a meaningful or a functional gene? Well, given that the average human gene length is around 8,500 base pairs, the answer is definitely yes. 20,000 base pairs is definitely long enough to code for not just one, but potentially multiple human fetal genes. So, in conclusion, number one, fetal DNA is indeed present in placental vesicles in extreme abundance. Number two, fetal DNA in placental vesicles are long enough, increasing the likelihood of carrying functional genes. Combined preliminary data suggests that functional fetal genes could potentially be delivered via vesicles into the mother's cells, essentially morphing the mother into a hybrid chimera with more than one individual's DNA. Therefore, moms, you are what your babies make you. So, I'd like to thank the following parties and people for making this project possible. Of course, my fabulous lab members, of course, and our two awesome supervisors, Professor Very Chamley and Dr. Sheree Blankering. Also, I'd like to thank the funding bodies of the University of Auckland Dockville Scholarship and Mastering Fund for Funding Our Project. Thank you very much.