End Of Year Funk-Two Week Action Plan!

As you can tell by the title of this post, I am in a bit of a funk as we draw close to the end of year. It has been an action packed second year of my PhD, my duties as President of my football club involved an immense load of issues and mental health challenges, and I have not had a Holiday since the end of 2016! 

It also probably does not help that in 15 days I am heading off to Canada and the US-going snowboarding at Whistler, football in NYC, Cursed Child on Broadway, Book of Mormon (for the second time, but first time on Broadway), Washington over Christmas, Universal Orlando, Disneyworld, and Kennedy Space Centre. 

So over the last few weeks I have felt little motivation to do work and have been feeling sluggish, tired and not following some of the self care goals I have been setting myself like going to the gym and eating healthy. 

Since I have just over two weeks at work before I head off, I decided it was a good idea to make an action plan on how I will get onto the right track, finish off the year well and actually do some work. 

GOALS TO GET BACK INTO THE GROOVE OF RESEARCH

  • Work out 5 days a week and get back to the gym. I have been pretty slack for the last month and cannot remember the last time I went to the gym! I cycle to the lab once a week and do a tap class once a week too but that is definitely not enough for me…especially when I do love food. 
  • Get into the office at 9am every morning. Since I am not doing any lab work and my days are mainly consisting of sitting at my desk writing my dreaded review paper, That also means I am sleeping in and getting into the lab at 10, or 10:30 or even 11. So i’m going to try to get an early start to the day in the time before I go away. 
  • Follow a morning routine. I was good at this in the middle of the year, waking up at the same time and taking time to drink a coffee and eat breakfast before heading to work. I’d love to get back into this and maybe even add in some stretching too as I would love to work on my flexibility. 
  • Be super productive in the office and when I feel unproductive, head home. This is one of the biggest things I advocate for and encourage. When I am work I work hard, don’t spend time on social media unless I have a 5 minute interlude. When I get to a point in the afternoon where I know I wont accomplish anything more then sitting at my desk on my phone, I always head home. So for the next two weeks when I know I am going to be having lots of desk days I am going to make the most of my time in the office and then head home to relax. 

So here is my action plan! Let me know if you are feeling the same at this point in the year and any steps you are taking to get back on track before the holiday break!

Advertisements

What am I Researching?-#30daysofpostgrad

We are 3 days into #30daysofpostgrad and I am still going strong (totally not because I spent all Sunday writing these blog posts). Today’s post is about why research and what my research question is. While I will not go into extreme detail, I’ll try to give the general description I give all of my friends and family when they ask me that exact question.

Why does chemotherapy not cure every patient?

That is pretty much the forefront question of my research. Chemotherapy is extremely effective in some cancer types, like metastatic testicular cancer which is able to be treated with combination chemotherapy. The cancer that our lab specialises in, Mesothelioma, is not so sensitive to treatment. What we also see is that not every patient responds the same, some that have similar cancers get cured by chemotherapy while some patients do not. And while there are genetic factors, differences in the stage and location of the cancer and some other differences between patients, there still might be something that is intrinsically different between patients that response and patients that do not.

This is where my project fits in, looking at why some people are cured by chemotherapy and some are not, using animal models. If we can find some commonality, like immune cells, or levels of vasculature or some other feature, we also want to see whether we can combine chemotherapy with some other drug to see whether we can improve the response in those patients that would not respond to the treatment alone.

I am nearly two years into this project and loving every moment of it. I am in the process of getting some RNA sequenced and from there will design the next few experiments of next year. I also have some really cool immune depletion data from this year that fingers crossed will link with the sequence data.


What are you studying? What is the focus of your research? Feel free to let me know as I love hearing about what other people are working on. 

7 Reasons Why I Research-#30daysofpostgrad

Welcome to day 2 of #30daysofpostgrad. Day 2 is all about why I decided to do my degree, in this case my PhD. I also decided to extend it to why I decided to enter into the cancer research field and what drives me to continue spending long hours in the lab and at my desk!

So I decided to write 7 reasons why I research, in no particular order…

  1. To make a difference. Sometimes it is really hard to see the big picture and how the endless hours in the animal house or in tissue culture labs will lead to helping peoples lives. I always think back to how Jim Allisons simple discovery of immune checkpoints has improved the survival of some really aggressive cancers like melanoma or how one of my supervisors has lead one of the worlds first clinical trials in mesothelioma testing a new treatment combination, and how even if I discover or report something small, every little bit helps lead to breakthroughs.
  2. I like learning things. I think this is pretty essential for most researchers, you have to like researching new things and broadening your knowledge. Just last week one of my results meant that I had to learn a whole lot about CD4+ T cell help, something I know nothing much about apart from the basics. After every experiment or every meeting with my supervisors there are 10 new things I have to check out.
  3. I enjoy solving problems. This is essentially what research is. Thinking of questions, designing experiments to test them, troubleshooting and then (hopefully) coming up with an answer. Designing experiments to test questions is probably my favourite thing to do!
  4. I love spending time in the lab. While long days can wear you down, I don’t think there is much better then writing up a protocol and sitting down in the tissue culture hood or at your lab bench and getting started!
  5. The community in the lab. I am so lucky to have a great group of honours students, fellow PhD students, RAs and post docs/senior researchers that are around me in our lab. The lab I am in is pretty big (around 30 people split into smaller groups) and everyone is helpful, supportive and enjoy sharing cake on a weekly basis.
  6. Presenting research to other scientists. Many people in my lab don’t like data presentations at lab meetings, but I love them! I love being able to share my data with the others in our lab and see what they think and get new ideas. Even though there are normally some pretty hard or outside the box questions that get asked.
  7. Talking about research is one of my passions. While I am just getting more involved in the science communication community online, talking about research and the importance of science is a passion of mine. Whether it is supervising students in the lab, giving tours or simply telling my friends and family what is going on in the research world, spreading the good work of my fellow scientists is so important!

I always love hearing about other peoples experiences and why they do research! So feel free to share with me in the comments the reasons why you research or work in the field you do!

How I ended up nearly 2 years into my PhD- #30DaysofPostGrad

I spotted this amazing challenge over on Instagram (@thescientistandhercats) and decided I would not only participate by posting pictures, but also by posting blog posts too. Both this blog (and my book blog) have been very neglected over the last few months so I am hoping this will get me back into the swing of writing!

Day 1 of #30daysofpostgrad is all about how I got to where I am now. Nearly two years into my PhD and loving the work that I am doing. My journey probably isn’t that complicated, but it just shows how you have to follow what you are interested in and be prepared to ‘fail’  before finding the correct answer.

HIGH SCHOOL

My high school experience was pretty normal. I studied hard, got good grades and was involved in a couple co-curricular activities. I don’t know what it is like around the world (though it has changed a lot since I graduated in 2012) but in Western Australia you do a range of all the subjected until Year 11, where you choose which subject to do for your final two years and in your exams. A lot of the university courses have prerequisite subjects too, so you have to take into account that as well as which subjects will get you the best entrance score (ATAR). When I was 15 I had my eyes set on either Medicine or Engineering, so I ended up choosing:

  • English Literature (I loved books and didn’t want to do the normal English which didn’t do Shakespeare).
  • Maths 3A/B (This was the highest  of the standard maths in YR11 and then you progress to C/D in YR12.)
  • Chemistry (I adored Chemistry so much!)
  • Physics (I liked all of physics apart from light/waves and electricity).
  • Maths Specialist (This was an additional maths course that is the highest offered. Since I wanted to do engineering this would save me time to prerequisites at University and I also enjoyed maths.)
  • Religion (It was compulsory at our Catholic school, but you could choose to do it and be assessed on it as an ATAR subject or as a non-ATAR subject and not have it contribute to your final score. I did the ATAR as I didn’t see the point in doing it without getting anything out of it for University.

I wasn’t fantastic at English Literature or Maths Specialist, but I got great scores in Chemistry, the standard Maths (doing the Specialist helped this immensely), Physics and Religion (which I ended up getting 90% in…I am good at writing what they want to hear.) Also note that I did not do any Biology courses during high school!

When it was time to get my ATAR, I needed at least 98 to get an assured pathway into postgraduate medicine (this means you can do whatever undergraduate course and then as long as you pass you have a place in the MD program) as I had already done an interview with UWA (The University of Western Australia). When my score came out as 97.85, I was pretty devastated that I didn’t get into Medicine. But with only a score needed of 80 to get into UWA, I decided to do my Bachelor of Science at UWA.

BACHELOR OF SCIENCE

I started my Bachelor of Science majoring in Engineering, with a second major in Pathology and Lab Medicine.  I wanted to become a mechanical engineer and work on Formula 1 cars, looking back I think I liked the idea of this as 6 years later I don’t even have my drivers licence and hate cars! I would do the GAMSAT and apply for medicine at universities around the country as well so I had the two options.

From the very first Engineering Unit, I hated it! It was taught so badly, based around group projects with people who were not the best teammates, I was one of the few girls doing the course and it was just so boring. I hardly studied and didn’t get the best marks. I did like the university Maths units, but the core Engineering and Physics units were the literal worst. What I did like was the biology and physiology units I did as part of my second major, especially as I had not done anything like it during High School.

My hatred of Engineering and love of Biology went on for one and a half years. After a terrible first semester of second year engineering units, I decided that the night before the second semester started I would change my degree, drop engineering and only do a single major in Pathology and Laboratory Medicine.

This was one of the best decisions of my life.

I loved the units, so I would study and get good marks. I had so much free space in my degree (along with the 4 units UWA makes you do that are not in your field to ‘expand’ your knowledge) that I did a German unit, an Ancient History unit, two Medieval History units and a forensics unit. I got to the end of my third and final year of my Bachelors degree with a decision to make. I did not get into Medicine (my GPA was terrible from my engineering units, but I did not in the top 8% in the GAMSAT) so what was my next move?

I had two choices (I couldn’t really get a job with the degree I had without doing a post graduate course.) I could do my Masters in Clinical Pathology which leads you into diagnostic labs or do my Honours year and get into the world of research. I would of course try to get into medicine again.

After looking at the pros and cons of the courses (and the fact that the Masters costs $30,000 compared to the $8000 of the honours) I decided to do my honours year. Then I had to find a supervisor.

Throughout this process I met with three supervisors. The first was a researcher working in mitochondrial diseases. She was nice and the project seemed OK, but I still wanted to explore my options. The second worked in stem cell engineering and the project had an engineering component in it too. We did an assignment similar to this in Undergrad but I found the supervisor to be very cold and not welcoming, and as an extremely anxious person having a supervisor who instantly felt supportive was important.

The last supervisor was working in cancer immunology and he gave two undergraduate lectures. The project sounded really interesting and he was so kind, welcoming and felt like someone who I could get along with and trust to help me through the year. It wasn’t much of a decision, but I ended up taking that honours project and in January 2016 I began my journey into research.

HONOURS YEAR

I am not going to write too much here as all I can say is that I loved research. My project was amazing, my supervisor was great and the whole lab environment was supportive and full of other students (both honours and PhD), research assistants and post docs that were friendly. I learnt a whole lot of skills during that year ; animal work, tissue culture and flow cytometry primarily. When it came to applying for medicine again, halfway through the year I decided that it was not for me (interacting with patients was one of the primary reasons why) and that I would stick to research. My supervisor continually hounded me to apply for my PhD in August, but I did not want to even think about the next year until I had handed in my thesis in October. As soon as that was done, I met with my Honours supervisor and two other senior scientists in the lab to discuss a potential PhD project and put in my application. I did not have much to go into the application apart from a presentation at a student conference where I won a price and was hoping that I would get a First Class which would guarantee an RTP (the scholarship provided by the Australian Government.) I did get First Class, and then I had to wait to see whether I would be funded.

It was the day that the scholarship notifications was supposed to be released and by 10pm I had not heard anything. I was constantly refreshing my emails hoping to get the email telling me that I was successful. By 11pm I was worried, but just after 11:15pm I got the notification in my inbox and was full of relief…though I don’t know why they had to torture me until late night to let me know!

MY PHD

I am now nearly two years into my ~4 year PhD and loving every moment of it…despite the stress, doubt and worry that I will never get it done. While I did not get too much data during my first year as it was optimisation and pilot studies, this year I got some really cool results and am just about to send the samples I have been collecting for 6 months (and had to optimise the model for 6 months before that) off to get sequenced which will provide a lot of data. The other students are great to work with and I am lucky to have a core group of supervisors (one of which is my honours supervisor as I stayed in the same lab.) I do miss having weekends as I often need to come in for my animal work. I also have my name on a paper from my honours project and in the process of writing a review (which has been two years in the making.) Currently I am keen on doing a post doc in America, but of course things might change (and America might change too.)


I feel like my story is quite simple and I was lucky to work out what I wanted to do with my life quite early (I am only just 23). But it just shows that everyone has different paths and different experiences that lead them to where they are. If I got into medicine straight away I would have never done my honours. If I didn’t do engineering I would never have realised how much I love biology and might have taken it for granted. If I didn’t meet with a range of supervisors I would never have found the project that led me to my PhD.

I am always so interested to hear other peoples stories so feel free to share in the comments or link to your own blog posts!

Saturday 28th September 2018- Day in the Lab #2

Hey everyone!

It has been a while since I have posted on this blog, and even longer since I have done a ‘day in the lab’ post. But recently I had a pretty full on day in the lab on a weekend and thought it was about time I shared another of my typical lab days.


I hopped on the bus just before 10am after heading to a secondhand book sale in the morning and ended up getting to the lab just after 10:30. I then headed straight down to the animal house to check on my mice. I then headed to the flow cytometer for 3 hours of sitting and running my samples. It was turned on and ready to go just after 11am.

I had 40 blood samples (and the respective single cell and FMOs) to run and it normally takes around 2-3 minutes for each sample. It was also Grandfinal day, but as I don’d really support wither the Eagles or Collingwood I wasn’t too upset at being in the lab and just watched it in the background as I was running my samples.

I was done just after 3 and then headed back to my desk to analyse some data and update some of my excel files for my ongoing experiments. I was starving so at 3:30pm I finally headed to get some lunch (a burger from my favourite place down the road from the office).
I was actually going to head downstairs to dose my mice (I have to do it in the night for my experiment timing) and decided to check my cells. Luckily I did as one of my flasks were confluent and if I didn’t split them today then they would be too confluent tomorrow and not be useable in my experiment.

I am pretty efficient at splitting my cells so 15 minutes later I was finally ready to head down to the basement to the animal house. By 6:45pm I was all done and ready to get on the bus and head home and straight to my bed to watch Netflix!

I always forget to take photos of everything so there was probably a bit more to show about my time in the lab. Hopefully I will get a bit better at documenting everything and I will post more of these before the end of the year!

Mental Fatigue in a PhD

Anyone doing a PhD or other graduate programs would be aware of the startling and concerning statistics regarding mental health and students and while there is much more awareness about this everywhere there are still some major hurdles every student has to overcome.

What I am feeling at the moment is what I am calling mental fatigue.

I have been doing my PhD for nearly two years now, and since I started I haven’t had more then a couple days off in a row and recently, I have been into the lab every day for the last two or three months. Sometimes it is not for more then a couple hours, but it adds up…especially when I look at my bullet journal and see everyday has some hours shaded in that I have spent at the lab.

While I do like what I do and love my project, it is tiring and ethically, I have to go into work on those days to check on my animal experiments so I unless I have no daily checks to do, I am always down in the basement collecting more data.

I also went straight into my PhD from honours, having about two months break and the most recent holiday was a weekend in Melbourne which was amazing but over a year ago and I have certainly earned myself at least a couple of weeks of holidays with all of the long days, nights and weekends in the lab. I am planning to head to America over the Christmas break and I am excited (I have yet to ask my supervisors though :/ )

But I digress, I was supposed to talk about mental fatigue which all of the above, plus the usual high workload and pressure that comes with a PhD has lead to me feeling very unmotivated for the last two weeks.

I had just finished a major experiment that required nearly two months of animal monitoring (half of that involved daily checks too), weekly flow cytometry staining and analysis and on top of the other three major experiments I am working on. I have collected some interesting data but the next steps is to repeat the major experiment in a different cell line and set up an even more complex experiment to work out some mechanisms. I am so excited to see what we find, but thinking about how much work it will be. Especially as the honours student who was assisting me with the majority of the monitoring will be finished soon. I also have to finish my review paper that is nearly two years in the making (and I should have published it last year) and stress about getting some extra things on my CV for future post docs and fellowships.

So this week I haven’t had the most productive of weeks. I have slept in until 9 am every day but Monday (and the only excuse is that on Monday I have my fortnightly supervisor meeting) and got into the lab at 11am. Today I left at 2:30pm as I felt so uninspired sitting at my desk and had gotten my lab work done and planned some next steps.

I have not done any more work on my review, read any papers and just feel like everyone else is doing so much more then me. I will also be at Jury Duty next week (I have no idea how long it will take) so next week feels like i’ll not accomplish much either.

But I am recognising that what I am feeling is normal and to be expected considering how much work I have put in. I treated myself to some lunch and coffee at a cafe to come up with a plan…while watching the office for the first time. As i’ll be in and out of the office next week due to Jury Duty, I’ll give you an update in two weeks time to see how I am going and share with you all what I did to try to overcome this.


Please let me know if you are a student, or were a student, or know a student who has gone through this or is tackling this at the moment. I would love to hear how other people deal with this and also other peoples stories!

Pharmacy (F)Phriday- Cyclophosphamide

First of all, if anyone can come up with a better name please let me know! Titles are 100% not my forte. It always takes me ages to think of a good title for presentations, posters and the one paper I am currently writing!

I am super excited to start this weekly feature on my (very neglected) science blog, titled ‘Pharmacy Phriday’ until someone suggests a new name. Each week I am going to feature a different drug or reagent I use in my day to day laboratory work.

The first couple of posts will be on different types of chemotherapy, as many people I talk to don’t realise that there are lots of different types that have different ways of killing cancer cells and other effects like activating the immune system. This weeks post is all about Cyclophosphamide which is the major chemotherapy I am using in my PhD Project.

What is cyclophosphamide?

Cyclophosphamide is a type of chemotherapy and is used to treat lymphoma, leukaemia, lung cancer, breast cancer, neuroblastoma (brain cancer) and sarcoma – though in many cases it is used to treat numerous other cancers as second or third line treatments. Cyclophosphamide is also unique in that it has another use ; to suppress the immune system. It is given to patients with an autoimmune disease or to patients after transplants when it is essential for the immune system to be suppressed so the donor organ is not rejected.

I’m going to focus on cyclophosphamide as a chemotherapy to cure cancer, as this is what I am looking at for my PhD project.

How does it work?

One of the foundations of chemotherapy is that most of the drugs target rapidly dividing cells, as that is when their DNA is most vulnerable as it is being exposed for it to be replicated (of course it is more complex then this). One of the ‘Hallmarks of Cancer‘ (one of the most ‘famous’ cancer papers around described the multiple characteristics of a cancer) is that the cells continually divide, far more then most normal cells. This means that chemotherapy ‘selectively’ target cancer cells, though other rapidly dividing cells like the lining of the intestines and the bone marrow are caught up in the crossfire.

Image result for hallmarks of cancer
The ‘original’ Hallmarks of Cancer. Some more were added years after the first publication, but I will keep it simple in this blog post. 

Cyclophosphamide is an ‘alkylating agent’ which is a class of chemotherapy. It attaches an alkyl group to the DNA which damages it. As well as proliferating more then normal cells, cancer cells also have fewer ways to correct any DNA damage or errors. When a cell detects DNA damage it triggers cell death, which can be controlled and regulated (called apoptosis) or unregulated. So all in all, cyclophosphamide adds an additional chemical group to DNA which damages it, causing the cancer cell to die. There is a pretty amazing story about how this class of drug was discovered that I will feature in a future blog post!

Image result for alkylating agent
Alkylating agents add on an Alkyl group which causes the DNA strands to link together and makes replication hard, leading to the cessation of cell division and cell death. 

Another thing about cyclophosphamide is that it is inactive until it is processed by the body, specifically the liver. This means that I cannot use the actual drug in any in vitro (outside of a living organism), instead I have to use one of its active forms. I haven’t had to do any in vitro experiments so far, but when I do I’ll face this problem.

Immune Effects of Cyclophosphamide

As a cancer immunologist, I have to talk about the immune effects of this chemotherapy! One of the major side effects is lymphopenia, which is a decrease in white blood cells. This is very commonly described in the literature (I also see it in my experiments too!) but it is not necessarily bad.

One important observation was that repetitive low dose cyclophopshamide can deplete T Regulatory cells (Tregs). Why is this a good thing? These Tregs act to suppress other immune cells, like our cytotoxic T cells that help kill cancer cells. There are a number of papers describing that when cyclophosphamide removes  Tregs from tumour and periphery, the other immune cells are released from being suppressed and are able to have an antitumour effect (here is one that shows that the depletion of Tregs leads to the activation of tumour specific T cells). Cyclophosphamide also has a large variety of other immune effects, but the depletion of Tregs is the most well described and clinically interesting as it is seen in both mouse and human studies.

How does it relate to my work?

Now I don’t want to give too much away (waiting for some all important publications to appear before I spill all the beans..though this may be a year away) but I am looking at how cyclophosphamide works to cure cancers in murine models and if there is anything we can do to make it work better. It is primarily in vivo work, which is a good thing as I would have to find some active forms of the drug to work with for any in vitro experiments.


This is the end of my Pharmacy Phriday post! I could have gone into more detail but i’m going to try to keep these features simple. Don’t hesitate to ask me any questions in the comments or share with me anything else you find interesting.