The Half Decent Pharmaceutical Chemistry Blog

A sunny Sunday might not be the ideal moment to fill some official papers for my official enrolment at Imperial College: 22 degrees and a cloudless sky are an inviting opportunity for an afternoon spent lying in the sun with a beer and a nice book.
I must admit while typing these words I’m thoroughly considering this as an excellent solution, but before eventually heading for a park with a can of Guinness and, why not, the forms I received from Imperial, I want to write a remarkably (hopefully) personal and, at the same time, useful post about Oxbridge and their application procedure systems.

Let’s start from the end: to apply for the position I managed to get all I had to do was to send an email to my (at that time) potential supervisor, with a copy of my CV and the name of at least two academic referees. He invited me to London for a formal interview, at the end of which I was already offered the job. The MRC (Medical Research Council) provided me with two nights accommodation at a lovely and incredibly homely guest house in Hammersmith, plus all my travel expenses were paid back.
Then, I received forms from the MRC itself, followed by those from Imperial and, finally, Leukaemia Research, which is the organization actually financing my project.

To sum up, because this is what this post is mostly about, I haven’t paid a penny.

Back in December, I applied for a couple of projects at the MRC Laboratory of Molecular Biology, which, as my future employer (CSC) is part of Imperial College, is formally a part of the university of Cambridge. Therefore, you need to submit two, separated applications: one to the LMB and the other to the “host” university.
Whereas the former, perhaps due to the fact that this is another MRC-based organization, was for free and, once invited for the interviews, both accommodation and travel expenses got reimbursed, the on-line application to the university cost £25. What’s more, outdated as it may sound, I had to (quickly) send a paper copy of all the papers and forms I had already electronically sent to them through the post: this means I had to ask my refs not only to send their reference letters via email, but also to print them out, put 3 (!) copies in a sealed envelop (together with 3 copies of other documents I had to fill in and make them sign). Those envelops had to be ridiculously signed on the outside, just  across the seal, and the signature was to be protected with a bit of sticky tape. All these complicated procedures were meant to prevent anyone (me?) from forging the precious content and to keep it secret to me (ha ha ha!).
Nevertheless, although pathetically old-fashioned, Cambridge was rather quick in letting me know the (negative) outcome of my application and the LMB was very kind throughout my staying at Addenbrooke’s for the interview. All things considered, thus, I may still look at them for a PostDoc.
Sadly (?), I cannot say the same for the rival counterpart: Oxford. Sure, their £25 on-line application system is simpler, more user-friendly, incredibly quicker to complete and it doesn’t even require a paper submission afterwards.
However, unlike my interview at LMB, I have no photograph of Oxford to show you as my interview was over the phone. I know this is not that unusual, but it still sounds idiotic to me (and I really do mean that!).
Even more infuriating was their timing. On leaving Addenbrooke’s, I was told a final decision would have been taken shortly and, whatever the outcome, they would have contacted me no later than a certain day (two weeks time, to be precise): I was told the result one before the deadline.

It took Oxford (dep. of biochemistry) more than a month to come up with an answer: by that time (interview on February 29, no news until April 3), I had already gone through my interview at Imperial, accepted it and submitted all the official papers to the MRC. To make things worse, after my phone interview (which doesn’t really give you any opportunity to know anything about the group and place you might join) I was told they would have informed me “at least within a week”.

Therefore, I can already tell you The Euchromatic Blog will be hypercritical to Oxford University.

It’s important, anyhow, to make absolutely clear that the position I’ve got is, by a large margin, the best one from many points of view (the only drawback is that I’d have liked to live in small, peaceful and full-of-students Cambridge rather than in a huge city such as London). I applied to LMB mostly because of its fame and then turned to Oxford and Imperial for opposite reasons: the former to try both sides of Oxbridge, the latter because of the project itself. In fact, I haven’t talked about the other successful applications I turned down because fortunately already with a gorgeous project in my hands (which means I won't go to Switzerland...).

The fact that this blog will close in July is putting me in the situation of having to find good pretexts to talk about all those remaining themes I had planned to discuss here, before I definitely leave the world of pharmaceutical sciences.

Surprisingly, one of these inputs was provided by a person who is, and will always be, one of my most hated individuals in the world: my pathology professor. If you remember, I already told you the story of when she called me out of the room the exam was taking place to tell me, vies a vies, I had an arrogant behaviour, that would have caused me disappointment in my life.
Well, you can imagine my reaction when I saw the following scene: she was trying to go out of the department in her car, presumably in a hurry, under heavy rain, but the only way out was closed by a parked car.

She then started to attract a lot of attention from everyone working in the buildings nearby by savagely and angrily blowing the horn and (but I’m guessing here) shouting and cursing and sweating and assuming some pricelessly infuriated expression.

This memorable scene went on for more than 15 minutes until she got the car removed and drove away. In the meantime, I was setting up a RT-PCR and only towards the end realised not only what was going on, but also who actually was sitting in that blocked car. So, I apologize for the poor quality of the photograph (taken with a mobile phone): with hindsight, I would have recorded the whole scene and put it on YouTube (and then posted it here).

Anyhow, the most important thing I could make out of this satisfactory moment is that it serves the right introduction to talk about intra-arterial chemoembolization.
Targeting is obviously something of paramount importance for any drug, not to mention those with a low therapeutic index. One of the parameters one could try to adjust when the only reliable pharmacological solution is poorly selective is positioning. Generally speaking, this can be direct, passive, physical (endogenous or heterogeneous) or active.

Chemoembolization (which is an example of direct localisation) isn’t probably the wittiest but I’ve always found the idea behind it simply brilliant. In a few words, a drug is introduced, as micro-spheres, directly into an artery that leads to the target.

As the name implies, this approach combines intra-arteriolar chemotherapy with embolization: the latter, a less immediate to understand concept, involves the induction of an occluding thrombus in order to prevent further blood supply to a tissue, such as a solid tumour.

The techniques is based on 0.2-0.6 mm diameter micro-spheres to deliver the drug: this particular delivery system is employed because of its size, which is just what it takes to block an arteriole. This results not only in massively accurate targeting, as the drug is released right where it must operate, but the effect is associated with a progressive block in the vascularization of the tumour.

Back in December, when I was frantically visiting one of my academic supervisors to make him sign official forms to back my application for a studentship, I was told the faculty of pharmacy was to award some money to particularly bright students. Unlike what generally happens in Italy, where grants are given on the basis of how poor you are (or, more likely, how poor you make the government believe you are), in this case it was all about the merit: number of exams taken, how quickly you’ve marched through them and your marks. Simple and fair, isn’t it?

Two years ago, I had been so stupid I didn’t even realise such a thing was going on (for the first time in the recent history of the faculty), while last year there was no money for such generous gifts. This year, though, I gave it a try. And guess what? I have make it: I’ve awarded on of the three €1,000 cheques. An amount of money predictably reduced once taxes will have been paid, but none the less a considerable sum, which I plan to spend almost entirely. First of all, I will get myself a proper digital camera, to finally take decent pictures for the next blog. Or, instead, turn to a video camera to turn myself into another, annoying, European, independent film-maker.
Plus, perhaps, a new, Euchromatic Blog-tagged iPod. Actually it may not have anything to do with technology: there are clothes, wines, etc. There are so many gratifying ways of burning your money these days.

It’s not only about the money, to tell you the truth: I’m pleased by the fact that, in the end, and on the verge of leaving this university, years of hard work yield some sort of financial feedback.

The news came as totally unexpected: the deadline was on March 3 or some and, in the meantime, some many things happened that I had almost forgotten about it, assuming that someone else had been given the award and the faculty hadn’t bothered sending a mail to the rest of the candidates (which is how people at Oxford university do when dealing with your application for a studentship).

By the way, feel free to share your opinions on the best way to invest this amount of money.

Last Wednesday I took part in an event the Students Association of the Faculty of Pharmacy organize every year: on two separated days, people from the fourth year are presented the type study done in the groups they could apply for carrying out their graduation thesis project. Generally, on the first day, it is “chemical” area to be under the spotlight, while the second day is dedicated to the “biological” one.

Theoretically, every year, every group leader should send someone. Anyone. In fact, although the (good) idea behind this event is that students who are in the middle of their project describe all the (sordid) details to their one-year-younger counterpart, apparently, it is far from being an unusual circumstance to have full-time PhDs to represent a lab.
Still, some times, a professor simply doesn’t care and no one turns up. This, in a few words, is what happened last year with my group: not having any pharma chemist there, my current supervisor should have done it, but she was just too busy and, predictably, not that committed to the cause.

This year, though, it was my turn. As a fifth year student, reaching the end of his job here, it’s hard to come up with a better profile. Or isn’t it? You see, the moment my group leader asked me whether I could work out a short (10 minutes) presentation for the occasion, I instantly saw a huge problem: since I had decided to embark on a molecular biology project during my third year and quickly communicated my intentions to my present group leader, last year I didn’t think for a second to waste a couple of lectures-free mornings to hear things I had been told already and, plainly, opted for staying in bed longer and go to a lab-course in the afternoon. This meant I had no idea what kind of information I was supposed to provide.

Neither the Students Association’s member to whom I wrote an email with my questions nor my lab mates helped. The former told me of some slides concerning the them of my thesis, the latter wanted me to focus on the techniques I am utilizing.

The result was remarkable and impressive: a perfect presentation for the day I’ll defend my thesis in front of the board. I realised I’ve collected such a quantity of juicy data, it wouldn’t be mad to start writing (perhaps just the introduction and part of the results), even though I literally cannot graduate before July.
Unfortunately, this brilliant and comprehensive presentation seems not to have impressed the students that much. Although a rather interesting drug, Teniposide, had a lot of attention. This drug has been a fantastic tool to address the question of whether a detected phenomenon of Topoisomerase inhibitor on RNA polymerase II was selective for Topo IB or not: teniposide (or, as it’s better known among my lab mates, VM 26) is a remarkably selective Topo II inhibitor, which is perfect for highlighting Topo I specificities. Moreover, teniposide is a useful clinical tool in the treatment of acute myeloblastic leukaemia.

As a brief reminder, Topo Is (as there are both IA and IB types) nick only one strand of a DNA duplex structure, while Topo IIs nick both strands. I’ve always found amazing that, despite being largely employed in many chemotherapy regimens, little is known about the mechanism of action of topoisomerase inhibitors. Giving molecular biologists a juicy research field.

Going back to my performance, I sincerely doubt that any one would choose our group (and molecular biology as a subject): both my short but accurate description of how a ChIP or a Real Time PCR work gave my audience a good idea about what I do, but I sort of suddenly lost them when words such as “promoter”, “siRNA” or “transfection” (inevitably?) came out of my mouth.

I already speak a different language (not to mention that all the slides were in English...).

Ladies and gentlemen, I am glad to announce the birth of my new project: The Euchromatic Blog.

As you can see, it is just an “under construction” page, at the moment, but I have obviously many ideas and projects for how it is going to look like once it will actually be in business. I would say it already exists in my mind. In fact, I am able to describe how it will be.

Right from the title, you can easily understand it won’t be a pharma chem thing, but don’t be fooled: it will not just be a molecular biology blog, but a proper scientific blog. So, in a nutshell, don’t think that it will be just western blots and micro arrays.
The idea is to take inspiration from the most successful and popular chemical blogs out there (Carbon-based Curiosities, The Chem Blog, Totally Synthetic and, why not, the Outrageous On-Line Uncle Al), mix them all, incubate over night at 37°C in culture medium (10% foetal calf serum) and see what happens.
Sure, if you have liked my pharmacology posts, you’ll find some of them, but the days of the “Saturday Night Synthesis”, I’m afraid, are dead and gone. (If anyone wants to start the series on their blog, feel free to do it: there’s no copyright involved, just give me credit for the idea).

One of the key words of the Euchromatic Blog will be “relax”: this must be a nice place to be, not a hall for lecturing readers. Thus, science will be discussed in a relaxed and colloquial way: radically different from how I’ve done here, especially in the beginning.
However, unlike this half-decent blog that I still like a lot, there will be many more real-world, bench stories from the lab. And much more personal stuff too

This very blog will get more personal too: not only will I advertise the new project, but a lot of attention is also to be given to me graduating and leaving this city and country.

Don’t worry, though: the end of this blog might have been scheduled, but the strength of its voice is far from gone.