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.

Reflections on second year

shallow focus photography of yellow star lanterns
Photo by 嘉淇 徐 on Pexels.com

This is my last week in the lab of 2018. It’s only really four days because we’re having our group’s Christmas party on Friday (laser quest and pub lunch) and then I’m at a conference on Monday before taking the rest of the week off before Christmas.

Towards the end of first year I wrote this post about how I thought first year had gone and I listed 5 things I wanted to change. In this post I’m going to see how I did with those goals and create 5 new goals for third year.

  1. Read more papers – I managed this one quite well. In first year I sporadically printed and read papers but this year I got organised and set up an RSS feed and have been pretty good at checking in with it most days – perhaps a little too often with my “inbox zero” tendencies. I use Mendeley to save anything I come across that might be useful for my project. I tried #365papers  and failed miserably though, partly due to me losing the spreadsheet I was keeping track of papers on in an IT nightmare but also me just not getting into a habit.
  2. Make more compounds – I certainly achieved this one. First year involved trying a lot of new chemistry and at the start of this year I optimised a lot of that chemistry making it far easier to get final compounds out. For example, one set of molecules I made last year took 8-9 separate reactions to get there and now with a small change to the chemical structure that I’ve learned doesn’t kill the activity of the drug in most cases, I can get to those compounds in 2-3 steps.
  3. Be more selective in the seminars I attend – In first year I felt I had to go to every single seminar to widen my knowledge but as you specialise you learn what interests you and what a good use of your time is. I still go to the odd seminar outside of my research area so I’m not in too much of a rabbit hole, but I certainly feel like I’ve been using my time a bit better when it comes to seminars.
  4. Attend more conferences – having only been to one conference in first year, I went to a few in 2018 – and still have one to go next week! I started the year by attending the Genome Stability Network Meeting in Cambridge in January, in March I went to the RSC-BMCS Mastering MedChem conference at University of Strathclyde in Glasgow, then RSC/SCI Kinase 2018 in May, again in Cambridge, and still have the RSC Biotechnology Group Chemical Tools in Systems Biology in London a week today.
  5. Use this blog more – this one I’ve technically achieved in the last month or so. Most of the year I found myself “procrasti-blogging” sporadically blogging if I was taking part in a science writing course where an assignment involved writing a blog or the Google Doodle of the day was linked to chemistry. Now I’m making a concerted effort to post regularly on here and also on my dedicated Instagram account.

I think I’ve done quite well in meeting all of those goals. They were fairly realistic goals without quantification. Now here are my goals for third year:

  1. Keep using this blog – weekly blog posts, a couple of Instagram stories/posts a week. Over Christmas I’m going to make a longer term plan for content and schedule as many posts as I can so it doesn’t take up too much of my time during term time. Let me know if there’s anything in particular you’d like to see.
  2. Get the desk/bench balance right – I continue to struggle with staying at my desk more often than being in the lab. Often I choose reading, agonising over lab book/write-up and writing off lab tasks to “tomorrow” that could be done today rather than making stuff in the lab. If anyone has any tips about this please let me know in the comments.
  3. Get something published – I have something to show for my research and I really want to get some of it published in a medicinal journal to show alongside my thesis at the end of the PhD. I’m waiting for some long-promised data from a collaborator which will help supplement my work but I’ve agreed with my supervisor that in February I need to start writing papers for publication without that research.
  4. Speak at a conference – similar to above, I have a sufficient story to tell that I would love to give a talk about just once about my research at a conference rather than just standing beside a research poster at said conferences where people may or may not come over to hear about it. I’d also like to go to a conference outside of the UK because travel is one of the perks of being in research.
  5. Finish the practical side of the project well – I plan to spend another year in the lab before writing up. I have until March 2020 technically but I’m leaving those three months as a “backstop” of sorts – #relevant. I have in my head I’d like to get to 100 final compounds for my thesis (I’m about two thirds of the way there so it seems tangible) and I’d also like to spend some time in the biology labs my group have testing some of those compounds.

Hopefully this time next year I’ll be writing a similar post about how well I did in achieving my third year goals. It’s crazy it’s got to my last year in lab already!

Did you make any goals/resolutions for 2018? Did you achieve them? If not, are you going to reattempt them in 2019? Let me know in the comments below.