Research@Cam: Timothy Lambden

This week I spoke with Tim-amisu Lambden, the NanoDTC's tiramisu master! If you haven't tried it out yet you're missing out! Throughout our chat, Tim spoke about his work at Cambridge, which included cyro-electron microscopy as well as the death of many, many flies... Keep reading if you want to find out more!

To start off Tim, could you tell me a bit about your PhD and what you get up to here at the Cambridge?

No problem! I'm Timothy, a NanoDTC student and my PhD focuses on electron microscopy and a technique called CryoSTEM, which is cryogenic scanning transmission electron microscopy. My PhD is focused on trying to image materials that are very susceptible to radiation damage, and in this case caused when under the illumination of the electron beam, creating a trade-off between resolution and damage. The materials I'm interested in imaging are materials that are very unstable and often very disordered. We can use CryoSTEM to better understand how atoms are organised on the nanoscale and cool them down to cryogenic temperatures to try and make the materials more radiation resistant when we are imaging them.

That's super cool Tim! I know you're in the same group as George Lewis, the second interviewee of this blog series. But it sounds like you do something very different. Is that common in your group or are you all working on the same types of projects?

We both share a PI who works on electron microscopy andhas done a lot of work on electron tomography more specifically, and within that that magnetic tomography, which George works on.

Overall there are many different projects in my group, all within the area of electron microscopy. As a technique, you can do a lot with it, and it's unparalleled in terms of the amount of resolution you can achieve. The materials I work on aren’t magnetic, so if you were to use magnetic tomography, you probably wouldn't get much information. But even though our research is quite different, we're both using electron microscopes, and collecting images using the same sort of equipment. It's also interesting to see what other people are doing in the lab, and even in the nanoDTC even if it's more removed from your work. There are themes and elements you can take from that that can help you.

And does that happen with your work, do you think, in your group?

Definitely! I think researchers are always learning and building upon other people's work in the past, this could be from within your lab, carrying on from research by other members or from other work published in the field. You’re able to learn from them and apply new knowledge and insight to solve problems. While research can often feel lonely, I don't feel like I'm working alone. I'm working with not just my own insight, but insight from my PI, people in the group and the field too, which is constantly evolving.

That's really insightful, do you think this is the case with all fields of science, like Biology, Chemistry and Physics? Are they all just learning from one another?

Yes, but it depends on the field. After studying Natural science at UCL, and specialising in physics and biology, I've had to be the interlink between biologists and physicists, and usually it feels like you’re speaking different languages. When you first start doing biology, it can be incredibly overwhelming. There are all these different words you don’t understand and all these strange techniques and experiments. Biology is just a weird, wacky world of different terminologies, all these different names of proteins and

genes and they are interacting in incredibly complicated ways that we don’t fully understand. And then in physics, you're working with equations and mathematical models which usually make some assumptions about a system for simplification.

I remember during my first internship I was working on a wound healing project in London. My internship was split between physics and biology. So, one of my supervisors was in the physics department and the other was in a biology lab. I wanted to do a project between the two as it combined both my areas of study, and I was interested in learning more about wound healing having had leg surgery the summer before, although that’s a story for another time.

In the biology department we were doing wound healing experiments. The model organism I worked with specifically was Drosophila (fruit flys) and we damaged the wing disc of these flies using lasers to investigate how quickly wounds heal and how switching genes on and off can affect that. In the physics group we were modelling this computationally and simulating wound healing and comparing this to biological experiments to see if they agreed. The aim was to develop new drugs to speed up wound healing and reduce scaring.

So you were working kind of between two different areas of science that I was quite different. How did you find that?

There was already some collaboration in the lab before I joined, which is good. But it was very different working with one supervisor compared to the other. The Physics supervisor mainly focussed on coding using a piece of software called Surface Evolver. And then in the biology lab, it's working with the flies themselves and performing experiments. One such experiment was a heat shock experiment, where we could express genes and turn them on by heating up the drosophila. Our first attempt at doing this experiment was a failure as the heater was too high and the drosophila all died of over heating, which is pretty sad.

Murderer!

I killed a lot of flies during the internship, I did feel pretty bad towards the end.

Sounds like two very different experiences working in each group!

It was and I think I learned two important lessons from this internship that helped me decide on what I wanted to do. In the simulation side, I quickly learned that you can basically simulate any result you want. So, if I wanted a result, I could just alter a few parameters. But the difficultly is justifying how these parameters are equivalent to changing experimental conditions to be accurate, as there's so many different factors involved. It was far quicker to alter the simulation and run a new simulation than do an experiment, so many experiments were first simulated first before attempting them. And then on the biology side, I learned there's lots of manual labour involved. Lots of repetitive experiments which were very time consuming. You need to go in every other day, sometimes on the weekend, to make sure the flies survive. I quickly realised I didn’t want to do a PhD in biology, as a result. Even though the science is cool, there's a lot of repetitive work involved, but often not much time thinking about a problem, just doing repetitive experiments instead to prove a hypothesis. I realised then that I wanted to do more engineering/physics focussed work, which led to another internship on electron microscopy.

I would agree, the science is super interesting! Your PhD is very technique focused on how to measure specific materials with CryoSTEM, what problems are you trying to solve using this technique?

Good question! One of my favourite quotes my second supervisor told me, not from him but someone whose name will come back to me, I forget! He's South African, he passed away recently, ah I can’t remember! Anyways, he has this quote “Progress in science depends on new techniques, new discoveries and new ideas, probably in that order”. So by developing a new technique, like X ray diffraction for example, you can do new experiments using this technique to investigate different materials So X ray diffraction of proteins for example and based on doing these experiments, you get new insights that can lead to new ideas and a new hypothesis, and in this case discovering mRNA, which gets read by ribosomes to create all the proteins in cells. It highlights the importance of technique development to create tools that make new discoveries possible. So, technique development can often help solve problems in many other areas. With my PhD being more focussed on being technique orientated than problem orientated compared to most other PhDs.

Wow I never thought of it like that! Do you think..

Sydney Brenner is his name! Sydney Brenner!

Well done to that! Knowing all of this, do you think the NanoDTC is designed with that in mind?

I think the MRes year in the NanoDTC is designed to be like that. it's designed to give you lots of exposure to different areas of research, but also equip you with all the necessary tools to succeed in a PhD when you do specialise. Although because it covers so much, it stretches you, sometimes a little too much.

I would agree! I don't know how you felt but I almost feel like I'm too spread out and I wonder did I make the right decision or should I just have just gone and started my PhD straight away?

Potentially. But that's only true in the case that you know what you want to do for your PhD. Most people that apply to NanoDTC don’t know what they want to do. Even I didn't know what I wanted, my interests were all over the place, and without the MRes year to develop my interests, I wouldn’t be working on what I’m doing now. I’ve always been very curious about lots of things, so it was inevitable my research interests were also similar.

I'm exactly like that too! I actually am finding it quite difficult at the moment to focus because everything here is almost too interesting! The NanoDTC has really opened up my eyes to so many different fields of science! When I think of people doing really well in their PhD so far, you're like one of the first people that come to mind you.

I'm surprised I gave that impression, but I don't know why I have! A PhD is very much a marathon not a sprint. One thing I think I've struggled with during my PhD is I have too much freedom. You can do anything, and you can lead the project in any direction you want, and it's an absolute luxury to have that. But when you're first starting off, it's like, I don't know what I'm doing! But once you understand the general running of the lab, how to use equipment, you understand what research problems intrigue you. You can take your project in any direction you want to do, and you have the freedom to do that but can take a while to get used too.

I think a lot of people forget that there is a human element to science as well. It's not just being stuck in a lab, just doing experiments, coming up with ideas and repeating it. The human element to research is very important and helps keep you motivated and engaged.

That’s really true Tim, I would one hundred percent agree! Thanks for chatting with me and sharing your work and experience so far throughout your PhD!

Proofread and edited by the one and only Larry Brazel!