What is your value?

What is your value?

Anyone doing a PhD will know that no matter how hard you try, sometimes it’s difficult to get out of the PhD bubble. This bubble I speak of is something I see surrounding so many students. We work, HARD! We work long hours to get data, supervisors put pressures on us, there are time pressure and most of us are guilty of putting undue stress on ourselves. It’s easy to compare ourselves to other students who seem to have it together (statistics would suggest they don’t!) and we aren’t able to see things in perspective.

Are you too caught up in the bubble? Go get that comforting cup of coffee, relax and lets reflect on you.

My question to you – how valuable are you?

I’m guessing that probably stumped you? Self-awareness and self-reflection are so important in developing a healthy perspective, but a lot of PhD students don’t do this. This PhD SOS blog post is all about realising what skills you’ve developed during your PhD and helping you realise how valuable these make you to future employers. Take a look at the following and think about how you’ve developed since starting your science journey.

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We’re managers as well as researchers

We may be undergoing STEM research but we shouldn’t only be labelled as a scientist, engineer or mathematician. We also become managers and leaders simultaneously which is awesome. Yes, we have guidance on our PhDs but we manage our own project, both in the experimental design but also managing the finances. It’s also very common that PhD students manage other people, such as students and lab visitors. As I’m sure many of you know, this can be very challenging but a valuable skill to have. Managing others comes hand-in-hand with developing time management skills. As another factor comes into your daily or weekly routine, you’ll have to plan which experiments of your own you’ll do when but also when you’re going to teach/help others in the lab. You’ll find yourself a master of organisation and prioritisation… hopefully!

 

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Oral communication skills

Think back to a presentation you had to do for your undergrad. How well did you speak? How nervous were you? Now think back to your most recent presentation. How have you improved? Do you feel more confident when you speak in front of an audience? A PhD offers many opportunities to speak about your data to others, both to small and large audiences. This could be in regular lab meetings, a departmental seminar, at a conference, or a competition like the three-minute thesis. Even explaining your thesis to your friends and family will help generate those all important science communication skills. Being able to explain complex science in a basic language takes practice. For those that work in a more clinical setting you’ll have to adapt the way you say things between colleagues and patients. Adapting to difference audiences is a great skill, and employers love the ability to adapt. It’s translatable to being able to work with different people and in different work environments. Another great way to develop communication skills is by teaching. Have you had any teaching experience? Is there any available to you? I’ve taught students of various backgrounds and levels of education in the lab but also undergraduates in physiology practicals. Seeking out those teaching opportunities will look great on that CV!

 

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Scientific writing

We get a lot of practice in this, it’s not all about the lab work. We attend conferences but to get there we have to write abstracts. The ability to write your introduction, methods, results and discussion into about 250 words or so can be very challenging! You’ll soon learn how to write in a succinct manner, otherwise that conference abstract is going nowhere. Some events and conferences ask for lay abstracts, reinforcing that skill of adapting to different audiences when we communicate. Then of course there are the bigger documents – that monster thesis and those all important science journal papers. Regurgitating all those results into concise words and reporting your results to fit journal requirements is a good learning experience.

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Analysis and problem-solving

We pretty much become experts at problem-solving. Science doesn’t work first time every time, as sad as that is! If your PhD has been hassle-free, I am 100% jealous. We try something, we analyse it, we realise it hasn’t worked (or isn’t optimal) and we have to come up with a new solution in the hope it will fix the problem and try again (and maybe repeat!). It will test your patience but a PhD will force you to manage it for sure. When something that hasn’t been working finally does you feel like a super scientist, you get that scientist buzz and a true sense of achievement! Having to practice and develop your problem-solving ability takes a lot of brain power, persistence and therefore a skill many companies value. It isn’t as easy process and shows you’re able to target a problem through logical thinking.

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Individual and team work

Your PhD is your project, no one else’s, and therefore most of the time you are working individually. It might be isolating at times but during these periods it does allow you to focus on you alone. Now, think about those moments when you’ve worked in a team. Does your lab group have communal tasks all members have to share in order for the lab to run smoothly? Have you collaborated with anyone? Working as a team can be so much fun but it definitely has its challenges. People have different ways of working, thinking and hold different opinions. The ability to work effectively in both settings will set you in good stead for a whole range of jobs. It’s so important to self-motivate and work by yourself, but also have the personal skills to work well with others.

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Character building

Now here’s the true self-reflection. Going through the PhD process will undoubtedly teach you a lot about yourself and you’ll develop new personal skills. A PhD is not like undergrad or a masters degree where you have multiple deadlines and only a short time to focus on one thing. You’re in the PhD for the long haul, and with that brings endurance and perseverance! You’ll also find you develop resilience to a certain point and ways to handle stress. Do you handle stress effectively? If not, maybe try different ways to improve this. Top tip, exercise! The PhD is a bit of a game really, it’s going to test you mentally and physically. Of course there will be times when you’re so motivated and productive you’re on a PhD high, but you’ll also go through phases where you feel a lack of focus. Have you found ways to manage those times of reduced motivation? What do you do to turn those negative feelings around? Having self-awareness of what makes you tick and how you work best are extremely valuable skills. You’ll learn a lot about yourself, and being clever with that knowledge is key.

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In research we bring knowledge into the world for the first time. That’s amazing! We often forget about how cool what we do is. We manage projects, we create, we problem solve, we discover, we develop in ourselves. A PhD is a journey and it brings a lot of value to us personally but to other people too.

A PhD isn’t just about generating good data. Remind yourself of the skills you’ve developed, it’s those that make you valuable to employers. Put those skills to your advantage.

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What skills have you developed during your PhD or science journey so far?

As always, comment below, I love to hear from you and your experiences!

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Enhancing placental function – my first publication explained

Enhancing placental function  – my first publication explained

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Four years after my Masters of Research in Maternal and Fetal Health at The University of Manchester, our paper is finally published in Theranostics which means I have my first science journal publication! As other scientists will know, this is a very exciting moment in our science journey.

 

The title is “Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling”. What does that mean?! In simple terms, it’s all about targeting the placenta in order to enhance its function by delivering therapeutic molecules to it. Science journals can be very inaccessible to non-scientists but it is so important we relay our scientific findings to the public. I’m going to talk about why an earth we did this research, how we did it, our results and what they mean… and hopefully it all makes sense and you’ve learnt something new!

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The background…

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Many serious pregnancy complications such as pre-eclampsia (high blood pressure and protein present in the urine), fetal growth restriction (FGR; baby is smaller than average) and macrosomia (baby is larger than average) develop as a result of suboptimal growth and development of the placenta. The placenta is the interface between mother and baby for nutrient transfer.

These conditions can lead to preterm delivery which in turn can cause complications. Babies who are born too early have an increased risk of developing cardiovascular and metabolic diseases, but there are currently no treatments available during pregnancy. Administration of a drug via an injection in human pregnancy can cause dangerous side effects and disturbances to the fetus’ development (teratogenicity). We all take pain killers for headaches from time-to-time right? You just pop them into your mouth, and the drug circulates throughout your whole body. This means at the site of pain, the drug is more diluted but may also result in unwanted effects.

This paper is therefore all about trying to target the placenta specifically with a therapeutic to improve placental growth and development. The human placenta has two different layers: the outer syncytium, which is the site of nutrient transfer, and the underlying layer of proliferating cytotrophoblasts (CTB). These CTBs are important for growth and supporting nutritional demands of the growing fetus. These cells divide, and fuse with the syncytium.

  • Low proliferation of CTB = FGR and pre-eclampsia
  • High proliferation of CTB = macrosomia

The rate of growth/proliferation is affected by various hormones and growth factors, but also regulated by small RNA molecules called microRNAs (miRs). These regulate gene expression and consequently alter various biological processes such as cell proliferation. miR-145 and miR-675 are known to cause a reduction in placental growth, and so inhibiting these could improve placental growth in the pregnant women. But how does this get around the issue of teratogenicity? Well, our group have shown it’s possible to deliver a therapeutic molecule, which is packaged in lipids (a liposome), specifically to the placenta with minimising unwanted effects in the mother and fetus. This is done by using a specific placental homing peptide conjugate (a link of small molecules that form the foundations of proteins) which selectively binds to the placental surface. Think of it as a molecular postcode for the placenta!

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So, put two and two together and in this paper we tried to use placental homing peptides to deliver miR-145 and miR-675 inhibitors directly to the placenta with the aim to enhance placental growth.

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What did we do?

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Testing the safety of miR inhibitor delivery

Ensuring that the miR inhibitors can be used as a clinical intervention for poor placental growth and development means prior safety testing. We need to make sure that their delivery doesn’t cause detrimental effects. We exposed pregnant mice to either a short or longer-term treatment of a fluorescent-labelled non-specific inhibitor. With a fluorescence microscope we visualised the presence and localisation of it (miR inhibitor in green) within the mouse placenta. Localisation of the miR inhibitor was found in the short-term treatment and also in the longer term one too.Results2 - fluor distribution writing

The miR inhibitor was not found in fetal tissues which is great! However, we found it localised in some of the maternal tissues suggesting a possibility of off-target effects – something that would need to be investigated further. The non-specific miR inhibitor didn’t cause a change to fetal or placental weight, litter size or the present of fetal abnormalities, so this indicates that it’s tolerated well in pregnancy… phew!

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Testing specific miR inhibitors in mice

Pregnant mice were either injected with a control solution (PBS), the non-specific (scrambled) inhibitor, or the treatments miR-675 inhibitor or miR-145 inhibitor.

Placental weight:

The miR-675 inhibitor did significantly increase placental weight. However, miR-145 did not. Despite this, interestingly a statistical test confirmed that it did reduce variability in placental weight. No placentas fell below the 10th weight centile for either inhibitor, which suggests they have growth-promoting effects.

Fetal weight:

Both miR-675 and miR-145 inhibitors increased fetal weight but the non-specific inhibitor altered the fetal weight distribution as well. At the moment, we aren’t too sure why. One potential reason could be species-specific effects, but if you want to geek out, check out the discussion section of the paper (link below) where other suggestions are discussed!

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We also tested the two specific miR inhibitors for any changes in litter size and number of miscarriages. Neither had an effect therefore further suggesting that this novel treatment is safe to use in pregnant mice, another step in the right direction!

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Testing the specific inhibitors in human tissue

Placental explants, which are chunks of fresh tissue, from first trimester (early pregnancy) and term (end of pregnancy) were cultured in the miR-675 inhibitor or miR-145 inhibitor with or without the placental homing peptide added on.  Both miR-675 and miR-145 with the peptide significantly increased the placental CTB cell proliferation, but so did their equivalents without the homing peptide, which was interesting. This enhanced cell proliferation was only found in first trimester placental samples.

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Summary

Without getting bogged down in all the intense sciencey discussion of this data (again, feel free to view the link for the actual paper below if you would like to read some more), what can we conclude from this study?

  • We provide evidence that the use of these homing peptides have a favourable therapeutic profile during pregnancy – they appear safe to use!
  • It’s the first piece of evidence for targeted delivery of a miR inhibitor to the placenta.
  • A homing peptide-miRNA inhibitor can be used to increase human placental growth in early pregnancy, which means it should be possible to manipulate the expression of those pesky placental miRs which contribute to pre-eclampsia and FGR.
  • This study suggests that these novel therapeutics may provide a new strategy for targeted treatment of compromised placental development and function.

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Of course further research is required to push the therapeutic potential of placental homing peptide-microRNA inhibitors further in the hope they will enter clinical trials in the future, but this study provides some really interesting data. Watch this space!

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You can find the original paper here!

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This was a much more science-heavy blog post than I normally write. Would you like more science explained posts?

Please comment below as always to let me know what you thought. Your feedback really is valuable to me. It helps me to grow as a science blogger and get the information out there that you like to read!

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