Walking in BRiDiT

The decision to build up this blog to narrate my experience as research fellow, did not really considered the fact that I have never been a blogger before, nor paid much attention to blogs in general.

In order to speed up with my research work, I have directed most of my time towards my research project so far, thus leaving little or nothing for my blog activity (yes, I still have the bad habit of sleeping at night, although I am surviving well with little or no social activity!).

So, even if the majority of the posts were written shortly after the situation described, they now sound mainly as a retrospective history of what I have been doing so far.
It is mandatory, therefore, to apology with you my readers (many I hope), for this delayed start: slowly, I will catch up with all the things I have done/learnt transforming this sort of past agenda in a real time event.

[Don’t tell anyone, but I am still trying to understand how the blog platform works ;) ]

As I was anticipating in other posts, I had previously stepped into glucose metabolism almost by accident and long time before committing to this research experience. I had worked only partially with pancreatic physiological models. I was not proficient in the techniques to be used, but I did possess the knowhow of what I was going to apply.

So, developing new competencies is exactly how I have spent my first 6-8months…

I don’t want to make the story long describing all the readings I had to do and listing every single method I had to learn, apply or simply revisit…but I feel mandatory to share with you a couple of techniques that are important pillars of my research project…so take this as a little preview of what is coming up in future posts!

“Because I want to go to fancy conferences!”

Ok ok…from my previous post someone might think that working in Science is all pain and no gain.

It is not like that, at all!

Nevertheless, it is true that we spend most of our time struggling to find how something works, to embrace with new concepts and try to figure how these fit with what we have previously learnt.

And it is somehow true that in some circumstances what makes a Researcher going is just looking forward for THAT DAY in which the numbers (as a result of an experiment) pile in a perfect, rationale, scientifically strong meaning! That’s real Joy!
[Priceless…while for all the other aspects, there’s a grant code!]

Indeed, speaking about a little bit of science-related fun, last month I attended a course on “how to become a Principal Investigator”.

The first question we were asked was “why would you like to be a PI?”

Moment of silence: what do we answer now?! How do we impress the others and make ourselves looking smart and not too nerdy?!

Well, with the facilitator’s big surprise (and most of the audience, indeed), someone answered in a very genuine manner: “because I want to go to fancy conferences!”

Well, we might agree or not on how/why we actually go to conferences and with what spirit, but this answer has reminded me that I have not told you anything so far about the conferences I have been attending.

Although I have been holding this position for little more than a year, and my background was almost everything but diabetes, I have had the opportunity to attend two important meetings so far: the EASD 2014 in Vienna and the Diabetes UK Professional Conference 2015 in London.

In both cases I had the chance to challenge myself as I was selected for short oral communications. The talks I have given were not directly related to the current project, but they have represented my first opportunity to present my piece of work to a diabetes-oriented audience…and guess what? I also ended up bringing home an award! :)

But the nice thing of conferences does not reside in standing in front of an audience celebrating our results (and hoping not to be grilled by the Giants of the field…which believe me, is everything but funny). The real pleasure is hidden in the hours after the conferences, where you engage with other fellows that share your same impressions, ideas, frustration and (eventually) joys…even if they belong to another lab in another city, another country and, why not, another side of the world.

No matter if you are a full professor, a young researcher, a post-doc, a PhD or just a master student: good memories belong to the post-conference chills!
It might be a pint, a dinner, a visit to a museum, a run for fund-raising, an event with restricted access where you sneaked in somehow…

and, believe me or not…this is where the best piece of collaborative works among members of spatially far institutions, becomes reality!

DUK photo cropped20140919_105153

And here comes the blog!

I find it kind of difficult to summarise my research experience via a blog.
Working as a researcher is not as simple as it appears: we don’t have “fixed” working hours (sometimes we work more than what’s on the contract!) or a fixed working schedule. Indeed, working in Science sometimes cannot be limited to a 24h capping: what we start on a morning does not necessarily end when we go home; it might continue for days, weeks and sometimes months, depending on the experimental setup! Thus finding the time to keep this updated is another interesting challenge.

I spent the first months to familiarise with the relative new workplace, to get along with the new supervisors, colleagues and all the staff to transform the new job into my daily routine. It was also mandatory and important to familiarise with the rules, duties, organisational chart, responsibilities, fund expenditure and, above all, the new research techniques and experimental models I had to learn and become proficient (and this is actually where most of my time has gone) …yes, I think you are beginning to understand it: the Marie Curie Intra-European Fellowship does not only consist of an intense research project, it possesses a strong component made of training, learning and all those aspects necessary to foster a young researcher’s capabilities towards scientific independence.

As part of this, I have also developed a series of outreach activities that see me involved in public activities, such as being a Marie Curie Ambassador, Volunteering for Diabetes UK as Risk Assessor, provide guided touring of lab to show our research and facilities to interested audiences…and, of course, write this blog!

What am I looking for?

The previous posts lead me to introduce my Fellowship project: I am exploring the role of some novel G-Protein Coupled Receptor (GPCR) signalling pathways (some particularly structured antennae whose signals and way of signalling is still to be clarified). I’m particularly interested in the physiology of the islets of Langerhans, which are clusters of cells in the pancreas that produce the hormone insulin. Where have you heard of insulin before? Of course, it’s that protein that is needed to regulate blood sugar levels and when there isn’t enough of it or it doesn’t work properly, Diabetes develops. Diabetes is a huge global problem, and around 400 million people worldwide currently have this condition.

My project aims to provide the molecular basis for the development of new medical tools based on the GPCR activity to prevent, treat and eventually cure Diabetes.

So, going back to our image of a cell as a spherical house, a GPCR is a particular antenna that crosses the dome many times. Yes…crazy uh! And if I ever mention a transmembrane territory (TM) in the future posts, you know I am referring to this dome-crossing feature.

This dome-crossing structure consists of 3 parts called the N-terminus (sticking out of the dome) and the C-terminus (sticking out inside the dome) and the transmembrane territories.

Proteins are made from small building blocks called amino acids that link into long chains. We refer to the ends of these chains as N and C termini to orientate the protein. So N and C work for biologists as North and South or East and West do for sailors (or tourists in the USA!)

If you remember the antennae structure, the N-terminal domain is capable to detect the signal (known to biologists as a ‘ligand’) on the outside of the dome, thus it is defined as the Ligand-Binding Domain, while the C-terminal domain is capable to initiate a series of event on the internal side of the dome that results in a specific effect within the cytoplasm.

So imagine that there is a currency in the cytosol. Signals are received by the N terminus and conveyed to the C terminus. The C terminus then can recruit effectors by spending its currency – this GPCR currency is called GTP. When there is no signal, the C terminus does nothing and doesn’t spend GTP and the receptor is at rest. The equivalent of the purse strings tightening.

So my aim is to consider how the cells respond to the money expenses through GPCRs, specifically those belonging to short chain fatty acids families which we think may be involved in insulin secretion mechanisms.

To pursuit these aims I have been appointed as Research Fellow at the division of Diabetes& Nutritional Sciences of King’s College London, as result of being entitled with a Marie Curie Intra-European Fellowship.

Looking for the other half of the Apple

Going now to the concept of a de-orphanised receptor, just imagine your house roof being equipped with as many antennae as it could accommodate, but for some of them you have no idea what information they’re receiving. If, by doing some tech work (or bio-molecular techniques if you prefer), the role of any of these “orphan” antennae is understood together with what signal(s) is being intercepted…well, you have de-orphanised the antenna..oops, the receptor!

It really means that something produced within the body (an endogenous signalling molecule, or ligand as we now know how to call it) is able to talk to a cell or a group of cells expressing the right antenna on the roof, resulting in a specific biological event taking place.

If this role turns out to be responsible for, or involved in, a disease, the receiving capability of the antenna (receptor, remember!) can be used to regulate the system from outside the body. In terms of scientific research, this means that we can use the receptor to control cell function, and this can lead to the development of new drugs, for example that specifically interact with particular receptors!

Signals and antennae

If you know what a receptor is, please knock on the screen!

Ok I have heard little sound…not really convincing though. I can tell there’s a bit of confusion. I can see your perplexed faces!

Cells might be described as medieval fortified cities, with walls (membranes) that protect their lands (the cytoplasm) with an important castle at the centre (the nucleus) where the king resides and dictates order taken from a written constitution (the DNA!)

Now, imagine this in 3D rather than 2D: the walls around the city are not a circle anymore, but they become a spherical dome and everything inside assumes mainly a globular form (thus becoming organelles). This little bubble-shaped city has controlled access through its dome (the plasma membrane) with gated doors/windows and apparatuses to interact with the external environment.

Well, membrane receptors are proteins that are “mounted” onto the cell dome, just like TV antennae and satellite dishes are on top of our roofs. Similarly to them, membrane receptors have the role of collecting signals from outside the cell and transferring the message they codify down to an apparatus like a TV or a decoding box: in our biological system this may lead to interactions with other proteins, initiating a signalling cascade recruiting and informing more players (like a video on youtube that goes viral via sharing) or the message might instruct the nucleus to make new proteins. Although one single antenna on a house roof is capable of receiving all the signals in the air and one TV apparatus can switch from one channel to another without the need of another antenna, this is not the case of a cellular system.

A cell possesses different antennae (receptors) for different signals, to be as specific as possible and not confuse the information sent across a specific channel [to be honest and fair it also happens that one signal can be received by two or more separate receptors or one antenna can get different signals…but this is another story…and I also promised not to allow things to get too complicated!]

If you think that traffic in London is nightmares…trust me, it is Paradise compared to the network trafficking within a human cell!

So, you might have learnt that the antenna is termed receptor in cell language…the signal that antenna is able to intercept is termed ligand instead!