PhD Update: 2019 Q1

This is the last year I’ll be spending in the lab before writing up my PhD next year. I thought it would be useful for me to blog where I am now and what I still need to do in terms of my research about once a quarter. Now that we’re at the end of March it’s time to review the last three months!

A selfie of me looking quite grumpy about some data I'm holding - a printout of a large table with lots of big numbers highlighted in red, orange and yellow

Third year started off with a bit of a rollercoaster. I had received some data back just before Christmas that I had been waiting about six months for. Most of the time I’ve been seeing how good my molecules are at shutting down one or two kinase enzymes. This experiment was slightly different in that it tested my six best molecules against hundreds of them – about 400 of the 518 found in the human body.

When I got the data back I thought it was bad news: the numbers were big for a lot of my kinases and I assumed that was a bad thing. I thought my molecules shut down far too many other kinases in addition to the one I wanted them too. This is typical of a kinase project because kinase enzymes are very similar in their shape.

It wasn’t the end of the world because I was still contributing something new to the field – you can’t drug my particular kinase. I started planning final experiments to make a few more compounds that would nicely round off my thesis to show I had tried all the sensible versions of my compounds as well as some potential new ideas to try and salvage my project.

Unfortunately, it took my collaborator who had organised the experiments a few weeks to get back to my e-mails for him to tell me I had my numbers mixed up! In this particular experiment, big numbers were good news! Very good news in fact! My best molecule only shut down 9/400 kinases.

Fiona looking embarrased with her hand over her mouth realising she made a mistake
Picture caption: Fiona standing in front of a redbrick wall with her hand over her mouth, realising her mistake

It was a huge relief in some ways that my project wasn’t, in fact, dead, but I was annoyed I had wasted a month taking my project in a completely different direction. What encouraged me though was the amount of stuff I had learned over the past couple of years and how I was able to come up with a few options for my project by myself.

Since then I’ve been working on some molecules that will round of ideally two chapters of my thesis, saying goodbye to two sets of compounds I’ve made that haven’t worked quite as well as the others. This has proved quite tricky as I’m trying to make a molecule no one seems to have made before – and as the weeks of failed chemistry go on, I can see why!

A gloved hand holding three sealed glass tubes containing failed reaction mixtures of black goop. Experiment numbers 165/166/167 written on the lids.
Picture caption: A gloved hand holding three sealed glass tubes containing failed reaction mixtures of black goop. Experiment numbers 165/166/167 written on the lids.

Once I get these molecules out the way I can focus on making smaller changes to my best compound to tweak it so that it only hits 1 kinase. That way when biologists use it they can be sure when things happen in the cancer cells they treat with my molecules, they can be relatively sure whatever change they see is due to shutting down that particular kinase.

I’m about to send away a set of compounds that will determine how long my chemistry route is going to be to each compound. At the moment, the best compound requires 9 individual chemical reactions to get to the final compound which is a lot of work for each compound! It’s because of a nitrogen atom present in a particular place that the chemistry is so longwinded.

I was able to make molecules that removed that nitrogen or moved it to another place in my compounds and swapped it for a carbon atom which reduced that chemical route to 3 chemicals steps! I’m hoping the version of the molecule where I’ve moved the nitrogen to a slightly different place will allow me to keep using a shorter chemical route, otherwise, it’s back to the long route I spent ages on in first year!

In the middle of March I attended a conference called Mastering Med Chem that was being held at the site of a pharmaceutical company called Eli Lilley based in Surrey, just a couple of hours up the road for me. I went to the conference last year and I was really encouraged coming across familiar faces and having a greater knowledge of the field in the talks I was listening to. To get a special discount I took a research poster with me and hovered beside it during coffee and lunch breaks just in case anyone wanted to talk about my research with me – which a few people did!

Fiona in business attire and wearing a conference lanyard standing in front of her A0-sized research poster summarising her PhD with a mixture of images and text. The poster title says "Design and Synthesis of Novel PRK2 Tools to Probe Cancer"
Picture caption: Fiona in business attire and wearing a conference lanyard standing in front of her A0-sized research poster summarising her PhD with a mixture of images and text. The poster title says “Design and SYnthesis of Novel PRK2 Tools to Probe Cancer”

Across all my channels (Twitter: @fi0n0 and Instagram: @thechemistryofaphd and on this blog) I started my #positperiodictable series where most weeks I post about an element of the periodic table to mark the 150th anniversary of Dmitri Mendeleev presenting his method for organising the elements to the world. I’ve managed to post the first 6 groups so far, 18 plus the f-block of superheavy radioactive metals to go!

I have also been trying to collect all the data for the molecules I made between October and December last year. I just have three more compounds to finish, then I can write up that bit of my thesis. I’m glad I’ve stuck with writing this part of my work up in thesis style, called the experimental section because it will save me a lot of time in the future.

So, in summary, after briefly thinking my PhD project was over, I’ve been trying to make some compounds that will round of large segments of my these I’m nearly there, and I think after the ups and downs of January, I don’t think I’ve been as motivated to be in the lab as much as I could have been but hopefully the next quarter will be better.

In terms of other things that happened this quarter, I enjoyed a short surprise holiday to Vienna with my partner, celebrated my 26th birthday, played in the Royal Albert Hall and got to do some fun science communication stuff on campus and in the London Science Museum so I’d say it’s been a pretty good few months. Just need to get on with the science I’m supposed to be doing!

Picture caption: Fiona holding a violin sitting on the stage of the Royal Albert Hall with her orchestra desk partner Ouli.
Picture caption: Fiona holding a violin sitting on the stage of the Royal Albert Hall with her orchestra desk partner Ouli.

How’s the start of 2019 been for you? Any highlights or challenges? Let me know in the comments below.

What’s on my lab bench?

Most people have a desk as a place of work. I’m lucky enough to have three workspaces as a chemist: my desk, my lab bench, and my fume hood, all for different aspects of chemistry research. Today I’m going to give you a tour around my lab bench!

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Picture caption: Fiona’s busy lab bench with different items labeled, from the sink to the sample vials!

My lab bench is used to carry out low-risk tasks involving my chemical samples. Most of the work I do when handling and manipulating my reactions is carried out in a fume hood to reduce my exposure to them but small analytical tests and sample preparation can b carried out on a bench – unless my sample is particularly smelly which thankfully not many of my compounds are!

I share a sink with another chemist in my lab where we wash up our glassware. We’re a bit like a student flat in that neither of us like putting the glassware away in the cupboards so take stuff directly from the drying rack which can turn into a mountain of conical flasks and beakers sometimes!

While I use an electronic lab book for my final write-ups, I keep a rough note of what I’m doing for each experiment in these blue and while notebooks and transfer it to the ELN at the end of the experiment. If I had to grab one thing in the event of a fire, it would be these notebooks as everything else I do is digitally backed up!

I keep final products in these sample vials before transferring them to smaller ones for archive storage about once a quarter. I draw the chemical structure on the yellow circular labels to help me find samples quickly. I try to keep my samples in chronological order but it doesn’t always happen so you’ll often find me hovering over these boxes trying to find vial such and such.

Although the picture doesn’t show it too well, I have to boxes of glass pipettes on my side of the bench, individual disposable glass droppers. I have a rubber atomiser that I attach to them when I need to transfer small quantities of liquid between flasks etc. and then the glass pipette gets recycled. We have two lengths of pipette and I seem to get through the shorter ones a lot quicker than the longer ones.

The tip-ex isn’t actually for correcting written mistakes in my notebooks – I tend to just scribble. I actually use it to mark sample lids so I can differentiate them as my own from my colleagues when using shared equipment. Our group has to use black lids for our NMR tubes so I found it a simple way to identify my samples from the dozens than go on the NMR instrument carousel.

I use a ruler for drawing straight lines on my TLC plates and for measuring the distance between spots once I’ve run TLC experiments (see my How do I know I’ve made the right molecule post).

The small tubes in the little beaker are how we store samples long term. They’re obviously a lot smaller than the glass vials and we typically have less than 0.1 g of a sample left after using what we need for future chemistry. We also use these tubes for transporting samples because they have individual bar codes on them. These are six compounds that I’ve taken out of archive storage for my colleague in biology to come to get whenever she needs them.

The conical flask on my desk contains empty NMR tubes, long skinny glass tubes used to prepare a sample for a particular type of analysis that investigates the magnetic character of the compounds – again see my previous post for more detail. The tubes are capped with the black lids I cover in Tipex.

I don’t keep many chemicals on my desk but these two are for a public engagement activity I’m doing with schools soon and so because they weren’t bought using the group’s research budget, need to be stored separately from the other chemicals I use, which are typically stored under my fume hood or in one of our several filing cabinets.

A calculator is a chemist’s best friend for double checking sample dilution factors and scaling reactions up to bigger quantities (like doubling a recipe). My electronic lab book does a lot of calculations for me but there are always some that need to be done manually like converting concentrations units from % to molar etc.

I hold on to my NMR samples until I’ve definitely got everything I need to write-up an experiment. Cleaning these tubes out isn’t the most fun job in the world so I tend to wait until I have a lot of tubes to clean before the repetitive task of rinsing them out.

My colleague and I share a number of things on our bench like sample vials and empty plastic columns for purification. We try to keep them topped up for each other.

Every chemist needs gloves for handling chemicals. I try to not get through more than a couple of pairs of gloves a day having mastered the technique of removing them in such a way that they can be worn again if I know I’ve been particularly careful and not got much on them.

My green tray has samples ready for being archived. I got this from a colleague who was leaving and it’s the perfect size for storing out mini sample vials. Scientists are a bit like vultures when they know there’s a free for all during a lab clearout or someone moves job, we become quite territorial about our pieces of lab kit.

My cardboard box has random bits and pieces in it like pencils and stickers for my lab vials.

I also have a mountain of plastic rings for storing round-bottomed flasks – spherical pieces of glassware that as you can tell by the name don’t stand up very well on their own.

Sometimes I get deliveries in the post in boxes that I bring into the lab. This tiny box was the perfect size for storing my TLC plates.

The laminated sheets are for writing the reaction schemes for what’s going on in my hood if I’m leaving a reaction on overnight. It allows colleagues and security to check a reaction is running at the temperature it is supposed to and hasn’t randomly heated up or cooled down overnight.

Lastly comes my vacuum pump which is attached to my rotary evaporator. My rotary evaporator, or “Buchi” as they’re named after one particular brand that makes them, is a bit like a kettle.  Attach round-bottomed flasks to it and boil off liquid solvents that I’ve dispersed my reaction in. The vacuum pump allows me to boil te solvents off at much lower temperatures than usual.

You may know about the phenomenon where water boils at a lower temperature at the top of Everest due to the reduced air pressure. My Buchi takes this to the nth degree by creating a vacuum and can actually boil water off at 40 °C! The samples sit in the water bath which is warmed to my desired temperature and rotates to maximise even distribution and mixing of my reaction mixture while also creating a thin film of solvent which then evaporates more easily.

The shelf above my bench contains frequently used chemicals for reaction work-ups/purifications. It includes various acids, bases, substances for removing water, stuff for preparing columns and my NMR solvents. We also have parafilm, a bit like clingfilm, used to seal vials and chemical bottles to stop samples or reagents from going off.

I hope you’ve enjoyed my lab bench tour. Stay tuned for future posts about my desk and fume hood.

What’s your working space like? Let me know in the comment below.

Science Conferences I went to in 2018

Over the course of a PhD, students are encouraged to leave the lab from time to time to go to conferences to learn about other kinds of research going on in their field. Science conferences gather researchers from academia and industry. In this post I will talk about the different conferences I went to in the second year of my PhD in 2018 and what I learned from them.

January – Genome Stability Network Meeting, Cambridge

The Genome Stability Network is a group of scientists interested in learning about how the DNA in our cells is damaged and repaired, usually with the aim of utilising these processes to treat cancer. At the start of 2018 I attended the annual meeting of the GSN and heard a lot of talks about different aspects of DNA damage and repair processes.

While I’m pretty sure I was the only chemist in the room – a lot of this work is carried out by biologists establishing the pathways by which these processes take place in cells – it was useful to see what themes emerged across the few talks.

March – Mastering Medicinal Chemistry, Glasgow

Picture caption: A metal sign at the bottom of some stairs pointing the way to the Mastering MedChem conference
Picture caption: A metal sign at the bottom of some stairs pointing the way to the Mastering MedChem conference

I had the opportunity to go back to my old university, University of Strathclyde, where I completed my undergraduate MChem degree for a medicinal chemistry conference aimed at early-career researchers. The talks covered a whole range of disease areas and approaches and I also took a poster summarising my own research to talk to people about during the coffee breaks.

I learned about new unconventional ways of finding starting point molecules (“hits”) to start new drug discovery projects, as well as hear from someone from pharmaceutical company AstraZeneca about a project similar to my own. It was useful to exchange ideas with the speaker to help my own project.

There was also a panel where the speakers were asked about their outlook on the future of the drug discovery industry, which I sadly learned was sounding bleak on all fronts. RxNet asked me to write a more detailed conference report which can be found here.

May – Kinase 2018, Cambridge

Picture caption: Fiona giving a presentation to a group of scientists in front of a slide titled "Designing PRK2 tools to treat cancer". The slide has pictures of enzymes and chemical structures, giving a snapshot of my PhD project
Picture caption: Fiona giving a presentation to a group of scientists in front of a slide titled “Designing PRK2 tools to treat cancer”. The slide has pictures of enzymes and chemical structures, giving a snapshot of my PhD project

The first two conferences were relatively general in their subject matter. In May I returned to chemistry for a much more focused meeting around kinases.

Kinases are signalling proteins (enzymes that tell a cell to do something) and are implicated in many diseases, particularly cancer. There are 516 kinases in humans so there are lots of opportunities to target them in different ways to treat patients.

I learned a lot about the different disease areas kinases are being targeted for as well as what the trendy kinases were that a lot of researchers seem to be looking at just now.

At this conference I got the opportunity to give a 2 minute, single-slide “flash presentation” about the poster I had brought. While having such a small amount of time to sell my research was challenging, I noticed a huge difference between the number of people who came over to my poster to chat to me afterwards.

If you’re attending a conference and are nervous about applying for such a slot I highly recommend it, it’s over in a flash and resulted in many more useful conversations about my work than if I hadn’t done it.

December – Chemical Probes in Systems Biology, London

Picture caption: the entrance to a stately building, Burlington House in London, with "Royal Soc of Chemistry" in gold above the door. There is a Christmas tree and an old lamp post next to the door.
Picture caption: the entrance to a stately building, Burlington House in London, with “Royal Soc of Chemistry” in gold above the door. There is a Christmas tree and an old lamp post next to the door.

At the end of the year I popped up to the Royal Society of Chemistry’s headquarters at Burlington House to attend the smallest of the conferences I have been to. There were roughly 50 people present and was very relevant to my project – the title conference alone would work as a thesis title for my project.

I’ve found it encouraging to note over the course of the last couple of years I’ve become familiar with “names” and institutions in my field. The first talk was by someone from the institute I collaborate with on my project and another speaker was someone I had previously applied to do a PhD with.

I had applied to speak at this conference but my application was unsuccessful. I was still able to take a poster and the collaborator I mentioned gave me some useful insight about some data I had been waiting a while for regarding my project.

Hopefully I will get to speak about my PhD at a conference in my third year – and it would be especially nice to get to travel abroad to a conference.

Have you been able to travel anywhere exotic for conferences in your line of work? Were they useful to attend? Have you ever given a flash presentation before? Let me know in the comments below.

Christmas may feel like its over but I have one more day of my #12DaysOfChemistmas that I’ve been sharing on twitter and instagram.

Chemistry PhD: A Day in the Life

I find people’s routines really interesting. Everybody’s different. Some people are early birds while others are night owls. Some people work long hours and others manage to fit a lot of work into a short period of time. In this post I chat about what a typical day looks like for me and the various things I get involved with both inside and outside of the lab as a PhD student.

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Picture caption: Fiona in a lab coat taking a selfie in the chemistry lab.

Day in the life:

0630: My alarm goes off. More often than not I press the snooze button for a little while.

0630-0700: If I’m sufficiently awake I go for a run then get ready for uni. I’m currently training for the Brighton Half Marathon at the end of February next year.

0815: Get the bus to campus.

0845-0900: Depending on how the buses are, get into the office, check e-mail and RSS feeds.

MORNING: I spend the morning either at my desk doing data analysis or in the lab running experiments.

1200: I eat lunch with colleagues. I usually bring a packed lunch but occasionally I treat myself to lunch at one of the university cafes.

AFTERNOON: I usually have a bit of an energy slump after lunch so I switch to low-brain-power tasks e.g. running TLCs in the lab or writing up analysis.

1600: I usually kick back into gear at this time of the day so I will have a burst of activity in the lab or at my desk.

1800-1830: leave office

Evenings: I don’t tend to do work on my PhD when I’m not on campus. In the evenings I’m either chilling at home, going along to something at my church or going to review something at the theatre.

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This is what a typical day where I have nothing in the calendar looks like. There are other things that pop up throughout the week which mixes things up. I generally prefer days when I have a meeting or two in the calendar. This is because it makes me more productive with my time because in my head I’m thinking “I have to get this done by X because of Y”. Below are some other things that are typical of chemistry PhD life outside of doing experiments:

Cleaning the Lab

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Picture caption: a set of super sensitive scales, known as a balance, reading 0.0000 g.

While everyone in my lab has responsibility for their own lab space, we have a rota for cleaning the communal areas of the lab. This involves checking our balances don’t have residual chemicals on them; cleaning up the TLC plate area; and checking our communal rotary evaporator for removing toxic/smelly substances has been cleaned.

Solvent Run

In a lab capable of up to nine chemists working in it at once, we get through a lot of chemicals, especially solvents! Solvents are the liquids we run our reactions in. Sometimes its water but its usually an organic solvent such as dichloromethane, tetrahydrofuan or an alcohol. We take it in turns to check our communal solvent stocks in the lab and top them up from the school’s central store as needed.

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Picture caption: multiple plastic bottles with different coloured lids containing different solvents.

Supervisor 1-2-1s

About once a week I sit down with my lab supervisor to review the chemistry and other work I’ve done, troubleshoot any problems I’m having and I propose what I plan to do next. About once a month I give a slightly “bigger picture” version of this project update to my main PhD supervisor. This helps me to build up a record of what I do on a weekly/monthly basis and gain input on my project from people with more experience than me.

Teaching

PhD students can undertake casual work with at my university to earn extra money. So far I have demonstrated in undergraduate labs – walk around and make sure everyone is carrying out their experiments safely and helping with any issues they have; invigilated exams; marked exam papers and taught tutorials and workshops for undergraduate chemistry/life science courses.

Attend lectures/seminars

As I am undertaking a research postgraduate degree instead of a taught one I don’t have any mandatory classes as part of my course. That doesn’t mean I can’t take advantage of the learning that’s happening around me on campus. Last year I attended a module called Fundamental Cancer Biology which helped me to consolidate what I’d learned about the biology side of cancer from my own personal reading which I found very helpful.

The life science school puts on a number of seminars that are mainly geared towards postgraduate students and research staff. While the term “seminar” can mean different things, in Sussex’s School of Life Science this session is usually an hour long where an in-house/invited speaker talks for about 45 minutes about their research followed by questions. It tends to be a very applied talk with only general concepts covered in the first few minutes. I enjoy seminars because you get the chance to learn about all kinds of research outside of your own.

Conferences

A few times a year I go to conferences. These are 1-3 day events where researchers in academia/industry meet in a specific location to hear talks about research around a specific area. I’ve been to conferences about medicinal chemistry, genome stability, the specific class of drug target I’m working on, and more! There’s a conference for everyone.

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Picture: Fiona giving a presentation at the RSC Kinase 2018 conference. A single slide summarises my PhD project with diagrams of chemical structures and biological processes.

While I haven’t had the chance to go abroad yet I’ve been to conferences on my own campus and in Glasgow, Cambridge and London so far. I sometimes take a poster summarising my research and am now applying to talk at some conferences now that I’m later on in my PhD. They’re a good opportunity to network and catch-up with people from my field of research.

Public Engagement

It is becoming increasingly common that researchers are required to demonstrate the impact their research has on society by communicating that research to the public. I’ll do a separate post about the various public engagement activities I’ve been involved in another time but very briefly, from time to time I take part in science fairs, schools events at the university and sometimes go into schools to talk about chemistry.

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Picture caption: Fiona pouring liquid nitrogen onto the floor, creating a large fog, as part of a public engagement show about chemistry at a school

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Juggling these things requires a lot of time management which I have varying levels of success at doing. I like that there’s a lot of variety in my work but primarily the goal of my PhD is to spend time in a lab making molecules. The other things give me a change of scene and enable me to develop other skills that will be useful for whatever job I do after my degree.

What does your typical working day look like? Is there an established routine or is every day different? Let me know in the comments below.