Ample sample but...no results.

Imagine for a moment the worst all-nighter you’ve ever pulled. Now times it by nine. Factor into that the fact that during this all-nighter you have to focus at 100% (or as close to it as is possible), you have to operate and move complex equipment, performing basic algebra and figuring out geometrical problems in reflective space. Congratulations you’ve just completed your first slot of CDI beamtime.

So science is tough. I knew this to begin with, however I didn’t realize just how tough. This week has nearly finished me off with a massive build up of stress, fatigue and disappointment. It’s a good job I’ve hardened myself to the rollercoaster of emotions through years of Ultimate tournaments.

Sadly things did not go our way this time, try as we might. It’s hard to stumble through those last few nights fuelled only by caffeine and pot noodles knowing you are unlikely to get results. We thought we’d prepared well but life always likes to throw us a curve ball from time to time.

 

I was actually really excited about this beamtime. Not only was I getting to play around with the equipment a lot more but we would be analyzing my sample this time. Or so I thought. Due to some unexpected equipment errors we spent about five days aligning, re-aligning, and then aligning some more. A bit rubbish really. Looks like my date with data was cancelled.

That means it’s back to the drawing board, and I do so love drawing. Or at least I love the scientific process, I’ve usually got a million and one ideas running through my mind and what is great about working here is no one tells you no. The research we are doing is very much frontier work so how can it go wrong when no one knows what is right.

Still planning doesn’t make for exciting blogging unfortunately so instead I’ve decided to dish up two exciting pieces of research from the world of Malaria. One of these has featured in the news quite prominently, and the other is pretty groundbreaking as well.

The first paper relates to the interactions between proteins at the surface of both Plasmodium falciparum merozoite, the parasite responsible for malaria, and red blood cells. These proteins are involved in the invasion of  blood cells by this parasite, the subsequent destruction of red blood cells by P. falciparum is what leads to the symptoms of malaria. As this disease kills millions worldwide year on year it is no surprise that falciparum is so intensively studied.

People have been trying for years to create a new vaccine for malaria however it has been a struggle. One of the big problems is that these proteins at the cell surface show a high degree of redundancy. A protein that is essential for one strain of the parasite to enter a cell will not be for another. This makes it difficult to make one vaccine that is effective for all P. falciparum strains and block malarial infection.

Enter the cell surface signaling lab at the Wellcome trust Sanger institute. This group have developed a very robust and effective technology for screening extracellular interactions. Here they express simply the external ‘stump’ of these proteins, the bit that sticks outside the parasite cell, as part of a more stable fusion protein. They then probe these with similar constructs of blood cell proteins. By linking this to a protein that can cause a colour change they could discern what binds to what.

What they found was a novel reaction between two proteins, PtRH5 on the parasite, and Basigin on the erythrocyte. This interaction proved critical in invasion, deleting PtRH5 from the parasites genome or blocking Basigin with an antibody almost completely stopped blood cell invasion.

 

So what’s the most exciting part? Well they tested this on not just one but all the strains of P. falciparum they had available and found the same result. This means produce a vaccine to provide resistance blocking this interaction could provide a reliable preventative treatment for malaria. It’s still early days yet but it is a truly fantastic result.

I am a bit biased of course. I actually worked with the group whom did the main body of the work during my year in industry. I actually remember the main author setting up the screens just before I finished. Interestingly they only worked 9-5 generally as they have a family, proof that it is definitely quality of work not quantity that pays of.

Ok next paper. This is one is also intriguing although I’d say it doesn’t yet have quite the human impact that the previous study does, probably why that one was published in Nature and this was not. This one concerned two topics particularly close to my heart. The cytoskeleton, something I’ve always been interested in, and Sickle cell anemia, because of my African heritage.

Sickle cell anemia is so named because of the odd elongated shape that red blood cells take when they become de-oxygenated. It  is a particularly nasty inherited disorder and leads to anemia as well as acute pain due to the bursting of blood capillaries that become blocked by these oddly shaped blood cells.

The cause of this is a mutation in the protein heamogloblin, the red molecule responsible for binding oxygen in blood cells. The single change in its sequence causes the hemoglobin proteins to clump together making the blood cell much more rigid. Whilst this is a debilitating disease it is recessive, meaning you need a copy of the faulty gene from both your mother and father, to express the symptoms.

So how does malaria tie into this? Well if in fact you only have one copy of the gene you do in fact show partial symptoms, not as severe but still somewhat uncomfortable. The upshot however is the added rigidity seems to convey some protection to malarial infection.

 

Up until now although there are plenty of theories dancing about no one was really sure exactly what the cause of this protection was. That is until a German group looked at the effects of this mutation on the actin cytoskeleton. Actin is one of the proteins that make up a network of fibrous molecules that contribute to the internal structure of cells.

When a red blood cell is invaded by the malaria parasite it’s actin cytoskeleton is reorganized to aid the delivery of a pathogen protein called adhesin to the cells surface. These proteins are, unsurprisingly given their name, responsible for sticking cells to surfaces. The over expression of this protein helps to prevent the destruction of the infected cells by preventing their entry into the spleen.

Through a powerful microscopy technique known as Electron microscopy these researchers discovered that the critical reorganization of actin in cells expressing the Sickle cell heamoglobin was blocked. This lead to a depletion of adhesion at the red blood cells surface and so they could enter the spleen to be cleared.

Whilst this does not have as obvious practical application as the first paper it is an excellent insight into the complex interplay of various cellular components, It’s quite amazing really that even 50 years after the protective phenotype of sickle cell anemia was discovered, only now are we gaining insight into how it works.

Makes me feel better about my lack of results anyway.

Ja, mata ne.

Coming to an understanding

So can you tell who the odd one out is? That's right it’s me, I’m the only one without glasses right. Ok this wonderful picture of my lab group aside I do stick out like a sore thumb in this country. This has been hardest thing to adjust to for me being from such a cultural melting pot as Britain I really don’t like sticking out so much, being in the minority when I travel about, the staring took a little getting used to.

I don’t want to make it sound negative, it’s not malicious or anything but I do feel my neck burning often. It’s something many people talk about, the ‘gaijin’ bubble. You never truly accepted out here no matter what your current status, language skill level, or who your friends are and after talking to a few it’s something that just doesn’t change.

It’s a little bit sad in a way, it makes it very difficult to meet locals as most don’t want to know or are afraid of looking foolish, as they can’t speak English so well. Most of the people I do meet are exceptional for wanting to associate with foreigners. It doesn't make them bad people, far from it, but it does give a rather skewed impression of the Japanese people as a whole. I’m sure this would change once I grasp the language a little better but after 8 months of being here I still feel like I’m watching Japan from inside a glass box.

This post is mainly stemming from the fact I’ve had little time to travel of late and therefore plenty of time for reflection. Sadly work has taken the forefront again, lots to do. Josie is still out of action and as yet I don’t know how to fix her. Also after a hectic week we have now started another slot of beamtime, 9 days our longest yet. It’s scary and tiring but exciting. My new samples are looking good and I really think we can take some good images.

 

So back to being an outsider, it’s not that bleak I guess, though sometimes the gawping from the school kids (particularly teenage boys) gets to me. It’s not a nice feeling for anyone and I don’t like being looked at like I'm an alien. Still I’m making some sort of headway. Sam and myself were actually approached by some of the staff at our local climbing gym the other day whilst struggling with a problem. So our conversation was pretty rudimentary but it was something. Slowly getting there I guess, just need to work harder, grow some balls and speak more.

Also I really do feel as though I’m starting to bond with my colleagues. I’m not sure if Koreans are just a bit more open, if it’s because my  boss spent some time in the states, or if it’s my continued hard work that's impressed them, but I definitely feel more included. I’ve also recently started learning the Korean language (the alphabet is awesome its like lego) so that may factor into it a bit more also. I think showing appreciation and interest in anyone's home culture will always endear you to people.

I’m not sure if these feelings will last, maybe I’m just on a low ebb right now. Over tired, over stressed and over worked. I’m not in bad shape or anything just fed up of being in the middle of nowhere. Perhaps things would be different if I lived near a city? I don’t really know and I guess I won’t anytime soon. At any rate for every bad experience I’ve had there are plenty of good ones to outweigh them. For the time being I’m still fairly happy with where I am. I mean look how pretty it is.

Right tant over I’ll talk a bit more bout what I’ve been up to recently. So as some of you may already know I’ve been trying to take my writing to new levels, particularily in the field close to my heart, trashy sci-fi. At the moment I’m working on a story for a writing contest put forward by a synchrotron in the UK called Diamond. As well as this I’ve submitted a story to nature, I’m pretty excited that the editor actually accepted it. Whilst that's by no means a publication at least it will get read.

I also tried my hand at a bit of scientific writing for the Medical Research Centre in London. They plan to put out a picture of scientific importance everyday of the year and they needed writers to pen the caption. Suffice to say I didn’t make the cut but I was thrilled at the opportunity to try and even got some helpful feedback.

Hopefully I’ll get to put some of this practice to good use soon as if this beamtime goes well I should have some data of my own to analyze and potentially publish. This time I’m hoping to look at one of my own samples, rather than one supplied by a collaborator.

My sample of choice is a preparation of microtubules, one of the three filamentous structures that contribute to the internal structure of our cells known as the cytoskeleton. Microtubules are large biological structures consisting of two proteins, alpha and beta tubulin, arranged head to tail in a cylindrical fashion. They are involved in all aspects of cellular activity, movement, replication, transport of materials and overall shape.

What is particularly interesting about them is a property known as dynamic instability. These complexes structures can rapidly assemble and disassemble within our cells in a very organized fashion. This is particularly important in events such as cellular migration, replication and differentiation which rely on the rapid movement of components within a cell at a much faster rate than can be achieved by diffusion alone..

The forces involved in these complex processes, from the linking of individual tubulins, organisation into single fibres and then the packing of fibres into bundles, are of great interest to many scientists, however there are a few problems. Firstly the process is call Dynamic INSTABILITY for a reason. The structures formed are very transient and so to image them you have to be either really fast or fix them in some way. Of course once fixed you lose a lot of important information about the process. Still the process of fixation itself isn't so well understood so there could be something interesting to investigate there also

The second is that whilst fairly long these things are also very thin. This makes it difficult to see any of the minor details of their arrangement particularly tricky. We are hoping that we can use the technologies we’ve been developing over the past few years to get a closer look at these stupendous strands. I’m not sure what the data will look like but I think we might be able to find something interesting out. Right back to work, all aboard the chirpy bus of wonder.

がんばるやん。

Ja mata Minna-san.

Get me the hell off this rock.

Seriously man what a month. There have been more ups and downs for me than Nemesis in Alton towers. Between beamtime experiments, most of which didn’t go too well, the Cheiron School and the passing of my Grandma, I’ve been totally physically and emotionally exhausted. I’ve also not had a free weekend in a month so the past one was a very welcome break.

In the past half a year that I’ve been here the 4000 miles between me and home have never felt as far as last week. At times I just wanted to curl up and sleep but I had to keep going.

The external pressures of work were definitely reaching into my psyche and when colleagues started to say things like “Is that enough for you?”  and, “You know I’ve noticed you don’t take much food.”, I realized it was time for a break to get my head screwed back on. Old habits die hard I guess.

Anyway before shooting on to the weekend I’ll backtrack to Thursday. My experiments with Josie last week did not go so well. I couldn’t take any readings as the DIT just wouldn’t work and being a team of two people we just ended up exhausted without achieving much.

So on Thursday Hikima-san, my colleague on this project, and myself headed to the local Izakaya Shunsai to commiserate our shortcomings. Exchanging an “otsukare sama” and a “kanpai” over a Kirin free and some food was a nice way to wind down and get to know Hikima-san a bit. We had a lovely chat over some food, the mochi bacon was definitely worth a mention. I learned a bit more about Hikima-san’s background and interests, in particular how he found moving to Kansai from Kanto and his fondness of home brewed beer something that is not so common in Japan.

Right so for the weekend I was determined to escape from the mountain. Arnaud was headed for Osaka to take a flight to Spain to attend an international conference so I asked if I could tag along. We were first going to a Mexican restaurant in Shinsaibashi for lunch with a friend of Arnaud’s before mooching about in Namba for a while.

At Shinsaibashi we met Arnaud’s friend, Mai, before ascending one of the nearby buildings for food. Japan never ceases to amaze me for its careful use of space. The building was pretty thin but each floor had it’s own tiny but fully functional restaurant.. They really know how to pack stuff in here.

The place was suitably Mexican with plenty of bright reds, oranges and yellows, tinkling acoustic guitars and interestingly writing all over the walls. Apparently some guy called Gen had been at our table two years previously. The place also seemed to be popular with the non-native contingent of Osaka. I picked Up American, Australian, British and Irish accents during our time there.

The food was nice, tortillas and beans make a nice change from rice, and also something with a bit of spice was very welcome. I was very glad Arnaud had invited me along, I don’t think I would of ever come across this place otherwise and I do love Mexican food.

So well fed and the conversations were rolling. Well sort of. I made an effort to speak as much Japanese as possible but my vocabulary is still frustratingly lacking. I can understand a lot but when it comes to expressing myself I always come up short. Admittedly Mai’s English was excellent but that's not the point really.

I’d voiced this to Arnaud before but what he said is right, I just need to practice more. I guess I make a lot of excuses, I’m too busy, I work with all Koreans, but they are just that. If I really wanted to I could speak better, I just need to practice more and ask more questions. I look stupider sitting there like a lemon than asking how to say something.

After killing about 3 hours in the restaurant, Arnaud was hesitant to leave due to his rather heavy luggage, we spent the rest of the time wandering through Namba and laughing at quirky shop names. I also had my first introduction to “プリクラ” (puri kura) short for purinto kurabu.

This is a phenomenon that whilst originating in the 90’s has managed to persevere in Japan, particularily amongst tweenaged girls. The premise is simple, insert your money and get your pictures taken. However the camera tweaks your looks subtly; emphasizing eyes, skin tone, mouth e.t.c. You can then add objects backgrounds and messages before finally printing the images as stickers. It made a nice souvenir at any rate.

At 6 o’clock we departed, bon chance pour la presentation Arnaud, and I headed to J-hoppers to spend the night. I’m just going to give this place a shameless plug now. It’s a hostel very close to Umeda station that I frequently visit. So much so that the staf recognize me by name and sight.

It really is a nice place. The staff are good fun and very helpful, the rooms and facilities are always clean, the location is great and best of all, it’s cheap. Right so enough advertising I settled myself in with some dinner and started watching the TV. It wasn’t long before I was joined by a couple of Japanese guests who wanted to change the channel. They put on a show called “Ippon Grand Prix.” I really didn’t understand too much but I think it was sort of like ‘whose line is it anyway’. They found it hilarious at any rate.

I moved upstairs eventually, tiring of the fact I couldn’t get any of the jokes and started chatting with a guy from Vancouver called Rob. Another reason I love staying in Hostels is you meet such interesting people. Rob is a freelance animator and had come to Japan, in his own words, because hey he’d never been to Japan, as good a reason as any I guess.

He was actually particularly interested in the art and had been picking out art books from second hand stores. He had a sketchbook to document his travels and kindly let me have a look. I’m always envious of people who can draw, it’s a skill I just don’t have. I guess words are just my means of expression. I had a good natter anyway before finally going to bed for a Good nights sleep.

At least that was the plan. Alas not to be. Unfortunately the guy sharing my room was a bit of a pleb. He strolled in at 4am bladdered, tried to hold a conversation for about 20 minutes before passing out and snoring the hostel down. I kid you not Nori, the manager, told me she could here him on the 2nd floor when she was cleaning, impressive since we were on the 4^th.

Still ever the philosopher, it was a disguised blessing as it gave me the opportunity to have more time exploring. I didn’t have much of a plan but thankfully due to the rain on Saturday a festival in Kyoto I had wanted to see was postponed until Sunday.

Since I was arriving so early, the festival began at 12, I decided to walk to th imperial palace from the station. Whilst it didn’t look so far on the map, never trust Japanese maps, it was actually an hour and a half walk. Still it gave me a fair opportunity to check out downtown Kyoto. It has such a nice vibe, totally different to the world of crazy that is Osaka and it was nice to experience a bit more.

On my way up I dropped by the Higashi Honganji temple. Honganji means primal, original or true vow depending on how you want to translate it, and it is the largest sect of Jodo Shinshu Buddhism in Japan. The complex itself is massive and the front gate, called the Mie-do, is in contention for being one of the largest wooden buildings in the world, it was quite impressive.

The main event began at the gates of the Imperial palace. The Jidai matsuri (festival of the ages) is a huge parade, which commemorates the end of Kyoto’s status as the capital of Japan in the 1800s. It consists of a parade of roughly 2000 people dressed in traditional costumes representing different periods of the cities history. It’s an awe-inspiring sight, especially given that many of the costumes are particularly intricate.

 I arrived to see huge crowds of people lining the streets leading from the palace to the Heian Jingu where the parade concludes. I was supposed to be meeting an acquaintance however she was yet to arrive in Kyoto so I decided to head towards the gates. The parade began dead on 12 o’clock with a group of men dressed as soldiers from the mid Meji period playing various instruments. The parade then takes us back in time from the 1800s back to the 700s when Kyoto was established as the capital.

It was an amazing a different way to get a view of Japanese history.  A bit more engaging than a museum or gallery for sure however as the announcements were all in Japanese I feel I didn't get as much out of it as I could of. Still I did finally get to see Geisha and Maiko, something I still hadn’t achieved since my parents visit.

I didn’t manage to meet my friend as planned, sadly the crowds were a bit intense, but instead met someone new. I noticed a young lady struggling to see over the crowds and let her go in front of me. Whilst I’m not tall back home I do have a good few inches on the average Japanese person and it’s great for situations like this.

We got chatting and I ended up spending the rest of the day with her. She was out in Kyoto for a year studying Japanese language and had been here about six weeks. It was nice to someone who was fresh in the country as I keep finding myself sounding a bit jaded and hearing someone’s fresh enthusiasm really helps bring the amazement back.

I love meeting new people, everyone’s got a story, and I also love a good gab so I was very happy she chose to stick around with me for the whole event. To my delight she was from England and from the North, a double whammy of nostalgia. It was nice to chat with someone from the UK it’d been quite a while.

The hours passed very fluidly, I was lucky to find someone as gabby as myself and with such different motivations and reasons for being in Japan from the norm. It was a fantastic day and as always nice to chat freely with someone my own age. It’s also inspired me once more to study the language a bit harder. I’ll get there in the end, “できるやんか“。しゃしんをみて、たのしんでください。

Mata kondo ne.