Most of us have heard of the immune system. “Oh, I’m a bit tired today, my immune system is run down”. But how many of us know exactly what an immune system is. Or what is does! This post is going to go through it step by step and hopefully by the end we’ll all have a better idea. I have to say immunology (the study of the immune system) was never my strongest subject. We’re all learning today!
So, first things first. Your “immune system” is not one cell but a collection of many types of cells that work to together to protect your body. I will be going through each cell type and their function. Just as a note “white blood cells” are another name for your immune system. In your blood you have red blood cells – which transfer oxygen around the body, plasma – which is the liquid part of blood that carries all sorts of things like hormones, glucose etc. and white blood cells – which are your immune cells.
Also, white blood cells are called leukocytes. (This is why I find immunology difficult…too much to remember).
So where are your immune cells made? The bone marrow! Immature immune cells (basically immune cells that haven’t learnt what they should do yet) are made in the bone marrow. They either do basic schooling there to learn what to do or they go to fancy school in the pituitary gland to get a full education. More on this later.
There are two types of immune system:
Your innate immune system is like a security guard walking around a museum. They are there to keep an eye on all the cells and deal with any small disturbances (such as the odd bacterial/viral cell). The innate immune system is made up of a number of cells. They are constantly going around your body patrolling. Innate immune cells can recruit other cells to the site of invasion and can also raise the alarm for a more comprehensive immune response. They do this by releasing signals called “cytokines”.
Here’s the list:
Mast cells: these cells reside in connective tissue and take part in wound healing.
Phagocytes (eating cells)
Natural killer cells: these cells kill normal cells that have been taken over by virus etc.
Gamma-delta T-cells (γδ T-cells): these cells are both innate and adaptive. Not much is known about these cells. Fun fact a PhD I know (Marina) studies γδ T-cells for cancer therapy. She took a blood sample from me and my γδ T-cells are really good at killing cancer cells.
A note on the immune system:
The typically immune response takes about 4-7 days to ramp up when the immune system has not seen the threat before. This is why when you have the flu it takes a full week or more to get over it. It’s also why you feel shocking. For the first few days while your adaptive immune system is metaphorically getting themselves together, the invader is running riot through your body.
When your immune system has seen the threat before (in the case of vaccines or previous exposure) your immune response it way faster. It will typically take 3 days for the immune system to kick in.
Fun fact! There is a layer of fat across your abdomen called the omentum. It kinda looks like an apron sitting over all your vital organs. The omentum is full of immune cells (all kinds) all the time. When you get major surgery, the surgeon will wrap the area with omentum to help with healing. It’s probably one of the most interesting areas of fat in your body (to me anyway). Another fun fact! Surgeries like liposuction tend to remove “good” fat (like what the omentum is) while leaving “bad fat”.
Your adaptive immune system is more complicated. Your adaptive immune system is not always active. They don’t patrol around at all time. In fact, your adaptive immune system is like S.W.A.T. It is activated when there is a serious threat and provides the big guns (as it were) to deal with the issue. Your adaptive immune cells (called T-cells and B-cells) are made in the bone marrow. They then travel to the pituitary gland where they are trained. This is where antibodies and antigens come in.
Antibodies are on immune cells whereas antigens are on every other type of cell. It acts like a hand shake. A cell will “put out their hand - antigen” and the immune cell will “take the hand - antibody”. If the antigen is recognised by the antibody nothing happens, and the immune cell moves on. If the antigen is NOT recognised by the antibody, then the immune system responds. Innate immune cells can present the antigens that were on the invaders they engulfed and this attracts adaptive immune cells to the site of invasion.
But the immune cells need to learn these handshakes.
The best example is blood types. There are many blood types – A+, A-, B+, B-, AB+, AB-, O+ and O-. These letters are antigens. So in a person with A+ blood type it means that on their red blood cells there is an antigen called A, whereas a person with A- doesn’t have the antigen called A. So in normal circumstances an A+ person will only have A+ blood cells. The immune system sees this and is fine. But if that person got a transfusion with say A- blood, the immune system will try to do the “handshake” but the A- blood cells won’t be able to. This is when the immune system goes into defence mode, destroying all the A- blood cells. This is called graft vs host disease and happens a lot with blood transfusions and organ donation.
Another example is vaccines. A vaccine is the antigen of the virus without the harmful parts. It allows the immune system to learn that the “handshake” is bad, which the adaptive immune system remembers. So if the real thing comes along the adaptive immune system can jump in immediately.
Here’s the list (lymphocytes):
Interesting fact: your immune system will also get rid of cells that have “gone bad”. Basically, if they are displaying abnormal behaviour, they can’t do the handshake, then they’re outta here!
Another interesting fact (I’m full of them), a fever is a tactic of the immune system. Most cell systems are very sensitive to temperature. A fever is a case of “sacrifice a few to save the many”. Your body temperature soars above the normal temperature for viruses, bacteria and your own cells. This helps kill off the invaders. You will lose normal cells and immune cells (and feel horrendous in the process) but the threat is gone! So yay!
The fun (?) part. Diseases associated with the immune system.
Numero uno! Allergies! When you have an allergic reaction, it is your immune responding to what it considers harmful. Now I really don’t know what is hugely harmful about pollen, egg yolk, latex, avocado and chestnuts (some of my wonderful allergies) but sure look. That’s what my immune system thinks. Now the degree of allergic response can go from mild (hives, vomiting, flu-like symptoms etc.) to life threatening (anaphylactic shock and death).
Second! Auto-immune diseases! These really is what it says on the tin. You know we talked about the handshake your adaptive immune system learns to distinguish your cells from invading cells? Well in the case of auto-immune diseases your adaptive immune cells are…well…not very good at learning. They attack your own cells.
Third! Cancer! Namely leukaemia (AML, CML and CLL), non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma. I will do a more comprehensive article about blood cancers, but these are all cancers of different immune cells.
Fourth! Cancer! Oh yes, your immune system can play a role in ALL cancers. Initially your immune system won’t recognise that cancer cells are bad and the cancer grows. Eventually the immune system catches on and tries to get rid of the cancer. But hey! Cancer is smart and uses Tregs and other regulatory immune cells (like tumour associated macrophages - TAMs) to calm the immune response. They can also change what antigens they present. And then they infiltrate the immune system (like spies) and turn the immune system within the tumour to their side. This helps the cancer grow, while also telling the rest of immune system to “move on, nothing to see here”.
The best part! We can use the immune system to fight back! Take that cancer!
This is what we call immunotherapy. We use the ways cancer manipulates the normal immune system and re-manipulates the now cancer immune system (is re-manipulates a word? Anyway you get me). There are a couple of ways this can be done.
1 – you shut down regulatory T-cells, basically preventing cancer from stopping your immune system
2 – you remove the antigen “handshake” on the cancer cells. This prevents the cancer cell from pretending it’s normal, allowing the immune system to kick in.
The problem with these two methods is it can affect your whole immune system, not just the one targeting cancer. This opens a can of worms in terms of knock on effects on your normal healthy cells. You do not want that!
But there may be a way of killing cancer and sparing your healthy cells. Some of your adaptive immune cells can be taken out of your body (via blood donation) and re-taught how to kill cancer. Specifically, your cancer. The white blood cells can be isolate from the rest of the blood and “primed” to know what handshakes your cancer is presenting. The army of cancer killing immune cells is the grown so there are enough to do the job and put back into your body. These primed immune cells go directly for the cancer, killing it while leaving your healthy cells to rejoice! Throw a parade! This therapy is still in trial phase but provides promise for more effective cancer treatment.
If you have any questions or comments, please don’t hesitate to contact me. If I have gotten anything wrong or missing information, please let me know!! It’s important we all get the correct information.
Just as a quick update!
As of 2.41pm Thursday 21st February I am writing my thesis! It's going. Writes itself really...
I wanted to do a quick post about what it means to be a PhD, what you have to do and how you become a doctor. Not a useful doctor mind but heck you've earned that Dr. in front of your name you tell the world!
I know I should have done this in the beginning but hindsight people!
What is a PhD?
You can get a PhD (or Doctorate in Philosophy for those nerds out there) in pretty much anything. If you have the will, the money and a supervisor you get that PhD in the history of snakes in Ireland. The majority of PhDs you'll hear about however will be in science subjects. Maybe some arts subjects (literature etc.) but the effort required to get a doctorate vs the usefulness to your future career means it's typically science-y types doing them. I am very happy to be told about any PhD's readers have done in any subject.
How Long is a PhD?
A PhD usually takes between 3-4 years however that changes wildly from country to country. For example in Scandinavian countries you are required to publish in a peer reviewed journals to be eligible to sit your viva (more on that later). In the UK and Ireland you are not required to publish. In the USA and Canada PhDs can take 5+ years and again some Universities will require you to publish before you get your doctorate. Again I don't know the rules for every country. My PhD is from Imperial College London and they have a max 4 year policy (unless there is some MAJOR need to delay your studies e.g. pregnancy). I am not required to publish. So my PhD is 4 years.
Who pays you?
There are a few ways of paying for your PhD. The usual way is by external funding. This can be from a charity or research council. Applying for funding requires a lot of jumping through hoops and a solid research proposal. The funding process is HIGHLY competitive and a lot of great ideas get left to the wayside. But there's a finite amount of money available and funding bodies need some sort of guarantee that the information generated will be useful for the future. If you feel this is unfair donate to your charity of choice if you know they fund PhDs. This is not an ad but CRUK runs a PhD sponsorship scheme. Another way of doing a PhD is self-funded! Oh yeah. You find the funding yourself or you pay yourself through. I have also heard of supervisors getting funding and they hire PhD students and pay them. It's slightly different from external funding because in external funding, it's awarded to the PhD not the supervisor. Your funding also decides how long your PhD will take. If you have 3.5 years funding you realistically should be finished in that time.
What is the funding used for?
There are three areas your funding goes into:
What does a PhD student do?
I have to say this (and it always gets me) while we may be considered students we ARE NOT students. It's like a job except not 9-5 and definitely not paid well enough. I never had to go to lectures and I never did exams. I could choose to attend lectures (for example I went to some MSc in Epidemiology lectures to learn about a subject I didn't know about). My department also ran seminar series and guest lectures for the whole department but again not mandatory. What I did was work 70+ hours a week in the lab and doing bioinformatics until I got some results I could write into a cohesive story. However I will note I except we are students when it comes to student discounts! You gotta use what you can!
How do you get your "PhD"?
You need to complete a set period of work (3-4 years) which you write into a thesis (in Imperial you do a max of 100,000 words). You then submit this thesis for evaluation and do a viva. A viva is a defence of your work. In my case, I will submit my written thesis to two examiners (an internal and external examiner) who are familiar in my field. They read the thesis and then we come together to discuss the results. I am asked questions and I have to defend my choices. It can take between 2-5 hours to do a viva defence. In other countries your defence is in front of a panel and is open to the public. So you could be standing up in a room full of people (grannys, children, your neighbour) and have to defend your thesis. Usually this happens in countries where you are required to publish. You are already peer reviewed so the defence is more general. One you complete your defence you are given corrections. These can be minor, for example asked to fix typos or a section of your written work, or (god forbid) major corrections, which usually require you to return to your lab/office/hell to re-do work or do more work.
How do I get a PhD?
The best advice I can give you is be open. There are a few ways to go about getting a PhD.
(1) You can pick subject(s) you want to study (I chose epigenetics and cancer) and research all the main people in this field. Contact these people and explain that you would love to do a PhD with them and would they have the ability to come up with a research hypothesis and apply for funding.
(2) Doing an internship/research assistant role in a lab you want to do a PhD in. You will have the ability to show your skills and know when the PI (principle investigator) is applying for funding etc.
(3) Go on www.findaphd.com/ NO JOKE! This is how I did it, I went on Find a PhD and searched my keywords. I found a PhD I liked the look of, got an interview and hey presto I got a PhD. Most labs will try to fill the position internally first (see point 2) but if they can't find a suitable candidate they will advertise publicly.
Is a PhD hard?
Yes. Next question. I joke. A PhD is hard as hell. It's meant to be. But it's also meant to be rewarding and you learn a lot, not just about your subject but about working in that environment and with other people.
What else do I get from a PhD besides a doctorate?
That is completely up to you. You make your PhD what you want. Some people will just do their own work and finish. I however did not do that and I encourage anyone thinking of doing a PhD or doing one to use your time. Teach, whether you do GTA work with undergraduate students or mentoring masters students. Teaching will give you so much in return (not just extra cash - always useful) but also new ways to communicating with others, new ideas and most importantly HELP! I have had three masters students throughout my PhD and if I didn't I wouldn't have the results I have. If you give time and experience to them, they will reward you. Trust me. I also did A LOT of research engagement, probably the most out of any of my peers. I literally said yes to every opportunity that came my way. Why? Because chatting to people about science is AWESOME! I mean come on I'm doing a science blog. It is just so rewarding. I also advise doing courses if you can, I participated in a MSc in epidemiology and did a number of Professional Skills Development Courses (like how to write a literature review, how to make a poster etc.) which really helped my writing and communication skills. As a PhD you are a part of a University or Institution. Use those connections to make the most out of your PhD.
Should I do a PhD?
Honestly I don't know. That is for your to answer. From my experience, if I had been honest with myself I would've probably not done a PhD. I was not and still am not mentally sound (in my opinion) to do a PhD. You require strength and determination. You will be knocked down a lot but getting back up and ploughing on will stand to you. Having said this I don't think anyone would've gotten the results I did or adapt their work the way I did. What you produce is unique and that's worth it. If you want to do a PhD and you really like your subject, do a PhD. Also we need more scientists in the world so if you're a science student wondering if you need to do a PhD PLEASE DO ONE! WE NEED YOU! Did that sound desperate?
What does your PhD mean to you?
I am not sure how to answer that question really. Stupid since I'm the one who asked it. I have a had a lot of struggles throughout my PhD. Struggles which as sadly not unique. I went back on anti-depressants, I had to deal with an eating disorder and I may or may not have tried on numerous occasions to hurt/kill myself. It sounds dramatic but mental health issues in PhDs are not uncommon. You are under a huge amount of stress and have to cope with doing things mostly on your own. This information shouldn't deter you from doing a PhD. I had mental health issues before I started. I may have struggled and I did have to stop my lab work early because I couldn't cope but I also would go back and do it again. I would do it better (obviously) but I would do it again. Doing a PhD has shown me (1) how smart I actually am, (2) what I am passionate about and (3) how strong I am. Plus who doesn't want to say "I'm a doctor" when asked on a plane if there is a doctor on board. Fair enough you do have to add that you in no way are you a medical doctor but god dammit you earned the right to say it!
So that's it! Again if you have any questions please don't hesitate to contact me.
Advances at the Interface Between Metabolism and Epigenetics
16th - 17th January 2019
This year I have the pleasure of attending the "Advances at the Interface Between Metabolism and Epigenetics" conference hosted by the Cambridge Metabolic Network in Cambridge, UK. This two day conference brings together scientists from all backgrounds with two things in common - an interest in metabolism and an interest in epigenetics. Funnily enough these areas interact a lot (which I learnt more about at this conference). When you focus on DNA methylation or histone modifications you forget where these modifications come from. Metabolism as a whole generates small molecules which can contribute to methylation (methyl group) and acetylation (acetyl group) to name a few.
What I have found most interesting about this conference is it's not just focused on cancer. While that's my research area (sort of) I have been to many (many) cancer related conferences. The focus is always "what does this mean to cancer?" whether we are discussing prevention or diagnosis or treatment. At this conference I am learning about the metabolism-epigenetic interaction purely out of interest in these interactions. Now I'm not saying I can't take this information and apply it to my work (which I will be...thanks #EpiMet19) but it's nice to learn something just to learn something.
The conference is two days long and covers a diverse range of sessions including:
Something else I found interesting (and bizarre) was the name "tags". The name tags were electronic and allowed you to "tap" another tag and share information. It also allowed you to vote on the posters you liked (kinda like a nerdy X-Factor). This is the brain child of Blendology (blendology.com/). This is a brand new way of building networks with fellow researchers. A very cool idea however you can't just "tap". It's more of a whack. This is slightly awkward with a stranger you just met!! Also do you really want to say "can I tap you?" or "do you want to tap?" ???
So all in all a really interesting conference.
OH! I presented a poster (again) on my wonderful work. I didn't feel there was a huge amount of interest but sure look! Metformin is an interesting drug with so much potential! If no one is interested it's their loss (this is what I'm telling myself as I weep into my poster because no one likes me! I joke.......sort of). To be fair I was in a bit of a dark area (as you can see in the photos) so maybe that's why.....
Jargon can be a big barrier between people from different career areas. The most obvious barrier for me that jargon creates is between scientists and the wider public but I also find that within the scientific community jargon is still a massive problem. For example when I am chatting with my sister (an incredibly talented doctor) we still find ourselves getting slightly confused about certain words we'll say. We're both technically in the area of biology and medicine but there is still difficulties in communicating.
When you start off in any subject you are given words and definitions and eventually those words just become part of your vocabulary. It becomes so ingrained in your every day that you lose the ability to properly explain what you mean. Honestly try remember the real dictionary definition of a jargon word you use everyday. Hard right? Now imagine you're chatting to someone who has no basis in your area and you're trying to explain the jargon word. Even harder! Why? because every word needs context. And this is where the jargon becomes a barrier. My way of explaining a jargon word ALWAYS ends up in me using more jargon. You end up either getting frustrated and sounding like an idiot OR even worse you end up talking down to the person you're chatting to.
So how do we combat jargon?
Well first thing is to acknowledge you use it.
The next thing is to identify key jargon words you would need to explain and practice how you would easily explain it. Easier said than done.
My scientific explanation:
Cancer cells up-regulate expression of oncogenes while simultaneously down-regulating tumour suppressor genes. Many of these gene expression changes are driver mutations associated with specific cancer types.
Now the tricky part is identifying how much your audience knows before you remove the jargon. You have to ask yourself - do they know what a gene is? Do they know what expression is?
If the answer to those questions is yes then you're in for an easier time:
Cancer cells can change the normal expression of genes by increasing expression of genes that help the cancer cells grow/create energy/create a good environment etc. while at the same time they decrease the expression of genes that would prevent the cancer cells from staying alive for example cancer cells turn off control of their growth so they can grow however much they like. Specific cancer types have gene expression changes in these pro-cancer and anti-cancer genes which can start the normal cells becoming cancer cells. These are called driver mutations because they drive normal cells into cancer.
If the answer is no you have to think harder about what you say:
Cancer happens when normal cells stop acting normal. They start to grow uncontrollably by making loads of energy and stopping themselves from dying. The way a normal cells becomes cancer is different in each cancer type and knowing these differences helps us treat cancer.
The trick here is to not try to explain every word but you completely change your approach. The three paragraphs all mean relatively the same thing.
Combatting jargon requires some practice but once you get the hang of it, it definitely becomes easier and easier. But why is it important? Well for a purely selfish reason it makes you better at writing scientific papers, communicating with your colleagues etc. For a less selfish reason it gives you an opportunity to share your knowledge with people who wouldn't necessarily have access to it. You can help combat the myths surrounding your area such as cancer research (there is not one cure all for cancer that doctors are hiding). You can also help people dealing with cancer understand what is happening to them or their loved one. People want to learn but it's frustrating when you don't know the language.
There are a lot of pros to doing more to combat jargon and being more engaging with the public. Whatever area you're in, give it a go. You might find you actually like the challenge.
As I said before in a previous post a couple of weeks ago (watch-this-space.html) I submitted a blog post to The Cancer Researcher-EACR Science Communication Prize. One of my submissions was shortlisted and has been published on their online magazine.
I wrote this blog post about research engagement and why it's important for scientists to engage with the public. We need to be better at discussing cancer and cancer research with a wider audience. Nearly everyone in the world has been affected by cancer in some way so everyone is interested in learning more. It's also a great way for scientists to be asked questions they have never thought of. Plus it's so rewarding to share what you do on a day to day basis.
Find the link below:
This can also be found on my External Work page:
Recently the European Association for Cancer Research (EACR), who as you know funded me to travel to IARC in Lyon to work, launched a blog competition. The idea of the competition was to write a short blog-style post about "Life in the Lab". You were allowed to submit as many blogs as you liked so I submitted three:
I found out today that the first one (Engaging with the (scary) public – why we need to do it and do it now) was shortlisted as one of the best blogs submitted. So while I didn't win, it will still get published in the next few months.
BUT what I also learnt was that they liked my other two so much that they are going to published anyway probably early next year! How awesome is that! Since they are going to be published I won't be adding them up here but watch this space. Once they become available on the EACR magazine website I will let you all know!
Yesterday I was at the New Scientist Live exhibition in the ExCEL London with CRUK (sorry I am terrible at taking photos so eh no evidence). My job there was to chat to the future scientists from 13 year olds to 23 year olds about how to get a career in research and what it was like to do a PhD. And my one biggest piece of advice was do coding! Bioinformatics is the future. Seriously, even if you hate maths (like me) learning some code language will help you in anything you do.
My other piece of advice was that if you want a PhD google www.findaphd.com/ because it does exactly what it says on the tin. It found me a PhD.
So what is bioinformatics and why is it important? Bioinformatics is basically the analysis of biological data. Biological data usually means sequencing data. You use a coding language such as R, python or unix to analyse this data. The above picture is my code for doing quality control on my RNA sequencing data using unix. I can also (barely) use R. To me python is a snake...
Bioinformatics is important because we can take massive amounts of data from hundreds or thousands of different samples and use this to generate more knowledge about areas such as cancer. This can be sequencing the entire compliment of genes in tumours of hundreds of patients to see if there are common mutations. This can tell us what these tumours have in common and what they don't. You can use this information for example to find "driver mutations" which are mutations commonly found in early stage tumours (p53 mutation is a driver mutation as some cancers require loss of p53 to develop into cancer).
The idea of using whole genome sequencing in cancer has come up a lot recently in the news. And the people who are taking this data and finding interesting results are bioinformaticians. Pretty much every cancer research lab in the world is generating data which needs to be analysed computationally. The data you get collectively from sequencing etc. is called "Big Data". However while most labs are generating this data, a large amount of those labs have no one to analyse it. We need more bioinformaticians to take this data and make it useful. Hence why bioinformatics is the future. The dawn of the era of joint experimental and computational scientists is dawning.
I am an experimental scientist (i.e I could barely use excel let alone do big data analysis when I started my PhD). But I had to learn how to use R and unix to analyse my data because frankly there was no one else. And this learning was something actively encouraged by my supervisor. Every PhD and post doc James has now can do both. It's very important to him. It really should be more important to a lot more supervisors.
So here's my experience: I have done two types of sequencing experiments generating data on DNA methylation (Illumina MethylationEPIC Array) AND gene expression data (RNA-Seq) of two non-cancerous cells treated with metformin. What this gives me in a massive amount of raw data (like hundreds and hundreds of gigabytes - the total amount of data generated from my RNA-Seq was roughly 2-3 terabytes...yeah). I took this raw data and ran it through quality control to make sure every piece of information I got is the best quality. I then ran analyses to determine if there are differences between DNA methylation levels or gene expression levels between your untreated and treated samples. For example if I see a consistent, large reduction in DNA methylation in a certain gene that suggests that there is more gene expression at that gene (low methylation = expression, high methylation = no expression). I can actually overlay this with my RNA sequencing data to see if that gene does actually increase expression! It's pretty cool. I mean you have to validate everything you see in your sequencing data with specific experiments but you can find some very interesting things. So what was the catch (besides learning how to make my computer do this stuff)? It takes time. It took me a full year to analyse my DNA methylation data and validate what I found. I have only started analysing my RNA-Seq data and I can tell you I have sat for 7 hours today watching my computer do aligning on my samples (it's only done 5 out of 9). And god forbid I put a comma in the wrong place or didn't add some arbitrary bit of syntax! I honestly spent a full day trying to figure out why the code I had written didn't work after the computer kept spitting out the "how to" file for the function I had used. I had done exactly what the were saying...except I didn't add two dashes, I had only added one. A bloody dash.
My take home message is the more information we have the more we know. Seems simple right? The gathering of that data is in the whole pretty easy to be honest and a lot cheaper than it once was (though both of my sequencing experiments cost a total of around £9,000 - £10,000 each to get the data). The challenge is analysing that data. Handling terabytes of data to find even one gene shows a change in expression is a mammoth task. We need more people who can pick up a pipette and run an experiment as well as analyse the results of that experiment.
If you are interested in learning any coding language there are lots of resources online as well as courses you can do. My supervisor (James Flanagan) and a fellow bioinformatician (he's a genius - Ed Curry) run a masters in Imperial in cancer informatics. It may seem daunting but if I can learn it so can you. And not just for cancer research or science in general. Knowing how to code could benefit a lot of industries.
Bioinformatics! It's the future people! Sure how are you going to programme your robot in the future if you don't know code??
Resources I found useful:
This year at the Imperial Festival, CRUK wanted to focus on multi-disciplinary research
The second demo was looking at the work the National Physics Laboratory (NPL) are doing on building the "Google Maps of Cancer". The NPL were CRUK Grand Challenge winners giving funding to expand this idea.
The idea is to bring together all the information we have about cancer to go from the whole tumour down to the molecular level. We can use techniques such as Mass Spectrometry to gather information about cancer for example different metabolites produced by cancer compared to normal cells. The demo ask participants to scan the QC code on the blocks. This led to a neat short video about how mass spectrometry worked. At the end you go a result (i.e. the colour the block should be). You turn over the block and leave it. At the end of the day there should be an image from all the blocks turned over.
For more information: http://www.npl.co.uk/grandchallenge/
Time done: 30 months
Time left in lab: 9 months
Time to write up: 9 months
Mood: wildly bouncing from euphoria to depression
So I thought I would do a quick update on how my PhD is going since it’s been a while.
I am officially ok with my hypothesis!
Before Christmas was the hardest my whole PhD has been. I had spent a year analysing and testing my Illumina MethylationEPIC array (which looks at over 850,000 CpG sites across the genome - not that many considering how many there actually are). I found sites that had significant increases and decreases in methylation when I treat with my drug, spent months validating them using pyrosequencing and what did I find? Nothing. It didn’t validate. It was soul crushing.
Buuuut I bounced back. Had a massive rethink with James (my supervisor). We thought about what my drug theoretically does and how that could affect epigenetics and I came up with a new, testable hypothesis. We were assuming my drug does a very specific thing that can be reproduced over and over (eg it always causes the same change in DNA methylation in the same place regardless of what cell line I use or how many times I test it). But maybe it’s not so specific but a bit more random, which is totally fine!
This new direction also means my Illumina MethylationEPIC array analysis wasn’t a waste of time. Celebrations all around!
And it seems to be going well so far. Well except that I have been troubleshooting the same western blot for nearly three months (and beating my head against a wall. Chairs may have nearly been flung through windows). There has been some tears not gonna lie. It’s hard to do the same 2-4 day experiment over and over to prove the result you got in the first place (in bloody January) was correct all along. Science - when you know you’re right but you have to show all the wrong ways to do it to prove you’re right!
So what’s the plan now?
Well I am going to the American Association for Cancer Research (AACR) Conference 2018 Chicago in April (there will be many vlogs, blogs etc) to present what I’ve found so far! Absolutely terrifying since I’ve only started to believe in my results like....last week.
I have about 9 months left of work in the lab before I need to write it all as a thesis. That will consist of learning a few new techniques (RNA-seq, ChIP-PCR) and to get a bit more of an idea of what’s going on and how I can sum this all up in a pretty bow.
I’m also getting another masters student to supervise (YAY) which I’m very excited about because I really like the project I wrote and the results regardless of what comes out are gonna be very interesting. She’s starting at the start of May and finishing up in September.
I need to write some papers! I apparently have to publish my data (who knew) so the next six months will be writing up what I've done so far in a paper, getting it peer reviewed by people in my group so I can find any holes and plug them before December. I can then sent the actual papers off for real peer review and (hopefully) publication.
And that's it. Sounds simple enough but it's taken 7.30am starts working 5-7 days a week to sum up everything I've done since August in a few paragraphs. I've even started drinking coffee in work. I shake violently when I drink coffee. It's not a good idea.
I have one last thing to say to anyone thinking of doing a PhD, to people currently doing PhDs or anyone living with a person doing a PhD:
To the person thinking of doing a PhD: be prepared. I want to scream at you "DON'T DO IT, IT'LL RUIN YOUR LIFE" but I won't. We need more researchers so we need more PhDs. But I will say be prepared. It is not all rainbows and unicorns. It's hard and it will drain the soul out of you. But then you'll get a result and feel like the smartest person in the world. You will love and hate the 3-4 years of your life doing a PhD. But really...be prepared to hate it a lot more of that time than you think.
To the person currently doing their PhD: you are a god damn hero. Keep going. You may feel like you're drowning or that "maybe a masters for this isn't so bad, I should give up". DON'T. You have given your blood, sweat and tears to this thing. You are going to finish. Even if I have to carry you. But seriously. You have got this. You are smarter than you know, you are incredibly dedicated and you will finish. No one knows what doing a PhD feels like until they have done one. No ones knows the soul crushing pain. I know. And I know you have got this.
To the person living with a PhD: please be patient. I know you don't understand what they're doing. I know you don't get why a little comma could cause a massive mental breakdown, the consumption of ALL of the ice cream and you getting shouted at but trust me there's a reason. It's hours, weeks, months or years worth of work that your loved one has just watched go down the drain (this specific example is for programmers but is applicable to all types of PhD). Just keep supporting and loving and caring for the lunatic PhD because they need it. And thank you for being there. Your presence means more than you will ever know.
PS: I know I haven't been posting a lot. I do apologise but every second of my waking life is going into completing my AACR poster so bear with me.
PPS: Apparently I have a very neat desk in my office and all other desks should aspire to look like mine......Weird email sent around the office!? So.....don't get too jealous everyone...
Cute animal photos keeping me sane are courtesy of the wonderful Fota Wildlife Park Ranger (Liam) supporting this lunatic PhD (me).
My name is Caitriona and I am a PhD student at Imperial College London, UK.