The Half Decent Pharmaceutical Chemistry Blog

I’ve created a new category for my future posts, “The Euchromatic Blog”, where to put everything related to the new blog. Today, for example, I feel the need to explain why, despite me being a co-owner of ChemBlogs, I have felt the need to register a web domain and use Wordpress.

First, Mitch, who actually had the idea of ChemBlogs as a platform for chemists willing to blog about their interests, has decided to close down the website as, well, I’m the only one who started a blog here (I wasn’t even that enthusiast about it) and has actually kept writing on it regularly. I could have gone solo and become the only owner of ChemBlogs, but I frankly can’t see the point of a (mainly) molecular biology blog, with the prefix chem- in the address line.
Moreover, nearly all the successful scientific blogs have their own, simple, address and domain.

The main reason for changing, though, has to do with spam. Yesterday I had been busy doing a Western blot, looking after cells and bacteria. Oh, and I also did one of things I like the most about molecular biology: a massive digestion with two different restriction enzymes, followed by a brief run on a highly resolving agarose gel.

Anyway, I could hardly check my inbox(es) every now and then, and certainly couldn’t check the comments to the blog I had to moderate. When I checked this today (after less than 24 hours) I counted 163 comments to moderate. As you can see, all of them have been cancelled because it was all spam. Today being Labour Day (or May Day: Wikipedia hasn’t helped me understand the difference), I have decided I have had enough of it: I’ve got better things to do than reading an endless list of spam messages.

This, though, doesn’t mean meaningful comments are not to be displayed after a while as usual: I just want to apologize for all the times your comments might be lost, simply deleted with the torrential flood of rubbish I receive.
You see, I believe both me and you don’t like this feature of my blog: you don’t immediately see your comment once it’s submitted and I have to dedicate a some time to go through the messages to fish for “real” ones. This badly influences the chances of people actually starting any interesting debate on what I write and, above all, is a bit of nuisance to me. However, of all the anti-spam plugins provided by LifeType, which powers this blog, this proved to be only reliable one, unless one doesn’t mind having tons of spam displayed among the comments to serious articles. Or needs to buy cialis or viagra or diazepam.

Wordpress has better systems of tackling the issue (I’ve tried them with another “draft” blog I’ve set up to work at the layout of the Euchromatic Blog) and many more toys to play with (perhaps even too many).

Summer is rapidly approaching and, apart from the warmer and sunnier days, if you’re a man, there’s a chance you have realised it by the sudden change in the diets of many women around you. Haven’t you noticed your girlfriend doesn’t you to take her out for dinner any more? Have you checked the ratio Diet Coke : Beer in her fridge? Haven’t most of your female colleagues at work started to sit around the table (where you have lunch all together) to eat, unlike you, carrots and yoghurt? Well, they are terrified, thinking about the day YOU will innocently propose to go the beach and they will have to squeeze themselves inside a microscopic bikini (perhaps, on that particular occasion they’d opt for a more forgiving swimming costume, pretending that it’s still too cold for them). Trust me, she hates you because you REALLY don’t care about your funny skin colour (after months in the lab, who could be bronzed?) and how fat you are.

Another common theme for a conversation among your female lab-mates (if you ever bothered listening) is the diet to try not to arrive…unprepared for the first Saturday at the beach. Magazines and tabloids are full of  last-minute, radical diets. Needless to say, most of these tips are for desperate, running out of time people and have no scientific rationale behind. So, they are useless and often dangerous.

Here at The Half Decent Pharmaceutical Chemistry Blog, we like to do things properly and, even when it comes to diet tips, we want to be taken seriously and put science behind what we say. So, for the diet I’m going to unveil for all the ladies reading this, I want you to believe me when I say I’ve tried it.

I’ve indeed what I call the Lowry diet on Wednesday and Thursday. In a few words, you skip the lunch break because you are in the middle of a protein extraction for a Western Blot: I know you’ll be thinking you should be in no hurry with the protease inhibitors and sodium orthovanadate and fluoride you have suspended your extract in. Don’t fool yourself, please: we all know you should be quick at boiling your samples and quantifying it (this, merely, because you’re curious to know how many microlitres you’ll have to load on your gel).
Whatever the reason, if you harvest at, say, midday (because it’s 24 hours after you performed a transfection), you’ll be right in the middle of your experiment, perhaps preparing your BSA standards for the calibration curve.
The Lowry assay, in fact, is a popular, maybe old-fashioned, certainly reliable and sensitive way of quantifying the concentration of proteins. It basically consists of two parts: in the former step you perform a Biuret reaction, which means you add an alkaline solution of Cu2+, that reacts with peptide bonds yielding Cu+ ions. Subsequently, Folin-Ciocalteau reagent is added: this mixture of phosphomolybdate and phosphotungstate undergoes a reduction to heteromolybdenum blue, which is coupled with the oxidation of aromatic amino acids in the presence of copper ions.

To sum up, the solution turns blue (picture to come soon, psi*psi) with an intensity that depends on the amount of tyrosine and trytophan and, therefore, the overall amount of proteins present in the cuvette. The precise concentration is determined by comparing the absorbance of the sample at 750 nm with those of standard solutions of BSA, used to draw a calibration curve.

This said, you generally need to wait 15 minutes after the addition of each of the two solutions, so you’ll be too busy to have lunch. It definitely works!

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.