Outreach means trying to engage the public with what we are doing in our research group. For me, this mainly means talking to non-specialists about our work and showing them around the lab. These non-specialists are typically interested members of the public and mainly supporters of the charity that funds work in my lab (Cancer Research UK). The most recent batch of activities have prompted this post on doing outreach.
Outreach is challenging. Taking part in these events made me realise what a tough job it is to do science communication, and how good the best the communicators are.
There are many ways that an outreach talk is tougher to give than a research seminar. Not least because explaining what we do in the lab can quickly spiral down into a full-on Cell Biology 101 lecture.
A statement like “we work on process x and we are studying a protein called y”, needs to be followed by “jobs in cells are done by proteins”, then maybe “proteins are encoded by genes”, in our DNA, which is a bunch of letters, oh there’s mRNA, ahhh stop! Pretty soon, it can get too confusing for the audience. In a seminar, the level of knowledge is already there, so protein x can be mentioned without worrying about why or how it got there.
On the other hand, giving an outreach talk is much easier than giving a seminar because the audience is already warm to you and they don’t want you to stuff it up. It’s a bit like giving a speech at a wedding.
The challenge is exciting because it means that our work needs to be explained plainly and placed in a bigger context. If you get the chance to explain your work to a lay audience, I recommend you try.
The big difference between doing a scientific talk for scientists and talking to non-specialists is in the questions. They can be disarming, for various reasons. Here are a few that I have had on recent visits. How would you answer?
Can you tell the difference [down the microscope] between cells from a black person versus those from a white person!?
For context, we had just looked at some HeLa cells down the microscope and I had explained a little bit about Henrietta Lacks and the ethical issues surrounding this cell line.
You mentioned evolution but I think you’ll find that the human cell is just too intricate. How do you think cells are really made?
Hint: it doesn’t matter what you reply. You will be unlikely to change their mind.
Do you dream of being famous? What will be your big discovery?
I’ve also been asked “are we close to a cure for cancer?”. It’s important to temper people’s enthusiasm here I think.
Are you anything to do with [The Crick]? No? Good! It’s a waste of money and it shouldn’t have been built in London!
I had wondered if lay people knew about The Crick, which is now the biggest research institute in the UK. Clearly they have! I tried to explain that The Crick is a chance to merge several institutes that already existed in London and so it would save money on running these places.
Aren’t you just being exploited by the pharmaceutical industry?
This person was concerned that academics generate knowledge which is then commercialised by companies.
My friend took a herbal remedy and it cured his cancer. Why aren’t you working on that?
Like the question rejecting evolution, it is difficult for people to abandon their N-of-one/anecdotal knowledge.
Does X cause cancer?
This is a problem of the media in our country I think. Who seem to be on a mission to categorise everything (red meat, wine, tin foil) into either cancer-causing or cancer-preventing.
As you can see, the questions are wide-ranging, which is unsettling in itself. It’s very different to “have you tried mutating serine 552 to test if the effect is one of general negative charge on the protein?” that you get in a research seminar.
The charity that organises some of the events I’ve been involved in are really supportive and give a list of good ways to answer “typical questions”. However, most questions I get are atypical, and the anticipated questions about animal research or embryo cloning do not arise.
I find it difficult to give a succinct answer to these lay questions. I try to give an accurate reply, but this leads to long and complicated answer that probably confuses the person even more. I have the same problem with children’s questions, which often get me scurrying to Wikipedia to find the exact answer for “why the sky is blue”. I should learn to just give a vaguely correct answer and not worry about the details so much.
The best questions are those where you can tell that the person has really got into it. In the last talk I gave, I described “stop” and “go” signals for cell division. One person asked
How does a cell suddenly know that it has to divide? It must get a signal from somewhere… what is that signal?
My initial reply was that asking these sorts of questions is what doing science is all about!
Two more amazing questions:
Is it true that scientists are secretive with their results and think more about advancing their careers than publicising their findings openly to give us value for money?
This was from a supporter of the charity who had read a piece in The Guardian about scientific publishing. She followed up by asking why do scientists put their research behind paywalls. I found this tough to answer because I suddenly felt responsible for the behaviour of the entire scientific community.
You mentioned taxol and the side effects. I was taking that for my breast cancer and it is true what you said. It was very painful and I had to stop treatment.
This was the first time a patient had talked to me about their experience of things that were actually in my talk. This was a stark reminder that the research I am doing is not as abstract as I think. It also made me more cautious about the way I talk about current treatments, since people in the room may be actually taking them!
With the charity I’ve been to Polo Clubs, hotels, country houses, Bishop’s houses, relay events in public parks. The best part is welcoming people to our lab. These might be a Mayor or people connected wth the city football team, but mainly they are interested supporters of the charity. It’s nice to be able to explain where their money goes and what a life in cancer research is really like.
To do these events, there is a team of people doing all the organisation: inviting participants, sorting out parking, tea and coffee etc. The team are super-enthusiastic and they are really skilled at talking to the public. The events could not go ahead without them. So, a big thank you to them. I’ve also been helped by the folks in the lab and colleagues in my building who have helped to show visitors around and let them see cells down the microscope etc.
Give it a try
Of course there are many other ways to engage the public in our research. This is just focussed on talking to non-scientists and the issues that arise. As I’ve tried to outline here, it’s a fun challenge. If you get the opportunity to do this, give it a try.
The post title comes from “Reaching Out” by Matthew Sweet from his Altered Beast LP. Lovely use of diminished seventh in a pop song and of course the drums are by none other than Mick Fleetwood.
We have a new paper out! You can access it here.
Title of the paper: The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle
What’s it about? When a cell divides, the two new cells need to get the right number of chromosomes. If this process goes wrong, it is a disaster which may lead to disease e.g. cancer. The cell shares the chromosomes using a “mitotic spindle”. This is a tiny machine made of microtubules and other proteins. We have found that the microtubules are held together by something called “the mesh”. This is a weblike structure which connects the microtubules and gives them structural support.
Does this have anything to do with cancer? Some human cancer cells have high levels of proteins called TACC3 and Aurora A kinase. We know that TACC3 is changed by Aurora A kinase. This changed form of TACC3 is part of the mesh. In our paper we mimic the cancer condition by increasing TACC3 levels. The mesh changes and the microtubules become wonky. This causes problems for dividing cells. It might be possible to target TACC3 using drugs to treat certain types of cancer, but this is a long way in the future.
Who did the work? Faye Nixon, a PhD student in the lab did most of the work. She used a method to look at mitotic spindles in 3D to study the mesh. My lab actually discovered the mesh by accident. A previous student, Dan Booth – back in 2011 – was looking at mitotic spindles to try and get 3D electron microscopy (tomography) working in the lab. Tomography works just like a CAT scan in a hospital, but on a much smaller scale. The mesh is found in the gaps between microtubules that are 25 nanometre wide (1 nanometre is 1 billionth of a metre), this is about 3,000 times smaller than a human hair, so it is very small! It was Dan who found the mesh and gave it the name. Other people in the lab did some really nice work which helped us to understand how the mesh works in dividing cells. Cristina Gutiérrez-Caballero did some experiments using a different type of microscope and Fiona Hood contributed some test tube experiments. Ian Prior at University of Liverpool, co-supervises Faye and helped with electron microscopy.
Have you discovered a new structure in cells? Yes and No. All cell biologists dream of finding a new structure in cells. It’s so unlikely though. Scientists have been looking at cells since the 17th Century and so the chances of seeing something that no-one has seen before are very small. In the 1970s, “inter-microtubule bridges” in the mitotic spindle were described using 2D electron microscopy. What we have done is to look at these structures in 3D for the first time and find that they are a network rather than individual connectors.
Nixon, F.M., Gutiérrez-Caballero, C., Hood, F.E., Booth, D.G., Prior, I.A. & Royle, S.J. (2015) The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle eLife, doi: 10.7554/eLife.07635
This post is written in plain English to try to describe what is in the paper. I’m planning on writing a more technical post on some of the spatial statistics we developed as part of this paper.
The post title is from “Pull Together” a track from Shack’s H.M.S. Fable album.
We were asked to write a Preview piece for Developmental Cell. Two interesting papers which deal with the insertion of amphipathic helices in membranes to influence membrane curvature during endocytosis were scheduled for publication and the journal wanted some “front matter” to promote them.
Our Preview is paywalled – sorry about that – but I can briefly tell you why these two papers are worth a read.
The first paper – a collaboration between EMBL scientists led by Marko Kaksonen – deals with the yeast proteins Ent1 and Sla2. Ent1 has an ENTH domain and Sla2 has an ANTH domain. ENTH stands for Epsin N-terminal homology whereas ANTH means AP180 N-terminal homology. These two domains are known to bind membrane and in the case of ENTH to tubulate and vesiculate giant unilamellar vesicles (GUVs). Ent1 does this via an amphipathic helix “Helix 0” that inserts into the outer leaflet to bend the membrane. The new paper shows that Ent1 and Sla2 can bind together (regulated by PIP2) and that ANTH regulates ENTH so that it doesn’t make lots of vesicles, instead the two team up to make regular membrane tubules. The tubules are decorated with a regular “coat” of these adaptor proteins. This coat could prepattern the clathrin lattice. Also, because Sla2 links to actin, then actin can presumably pull on this lattice to help drive the formation of a new vesicle. The regular spacing might distribute the forces evenly over large expanses of membrane.
The second paper – from David Owen’s lab at CIMR in Cambridge – shows that CALM (a protein with an ANTH domain) actually has a secret Helix 0! They show that this forms on contact with lipid. CALM influences the size of clathrin-coated pits and vesicles, by influencing curvature. They propose a model where cargo size needs to be matched to vesicle size, simply due to the energetics of pit formation. The idea is that cells do this by regulating the ratio of AP2 to CALM.
The post title and the title of our Preview is taken from “Zero Tolerance” by Death from their Symbolic LP. I didn’t want to be outdone by these Swedish scientists who have been using Bob Dylan song titles and lyrics in their papers for years.
We have a new paper out! You can access it here.
The work was mainly done by Cristina Gutiérrez Caballero, a post-doc in the lab. We had some help from Selena Burgess and Richard Bayliss at the University of Leicester, with whom we have an ongoing collaboration.
The paper in a nutshell
We found that TACC3 binds the plus-ends of microtubules via an interaction with ch-TOG. So TACC3 is a +TIP.
What is a +TIP?
This is a term used to describe proteins that bind to the plus-ends of microtubules. Microtubules are a major component of the cell’s cytoskeleton. They are polymers of alpha/beta-tubulin that grow and shrink, a feature known as dynamic instability. A microtubule has polarity, the fast growing end is known as the plus-end, and the slower growing end is referred to as the minus-end. There are many proteins that bind to the plus-end and these are termed +TIPs.
OK, so what are TACC3 and ch-TOG?
They are two proteins found on the mitotic spindle. TACC3 is an acronym for transforming acidic coiled-coil protein 3, and ch-TOG stands for colonic hepatic tumour overexpressed gene. As you can tell from the names they were discovered due to their altered expression in certain human cancers. TACC3 is a well-known substrate for Aurora A kinase, which is an enzyme that is often amplified in cancer. The ch-TOG protein is thought to be a microtubule polymerase, i.e. an enzyme that helps microtubules grow. In the paper, we describe how TACC3 and ch-TOG stick together at the microtubule end. TACC3 and ch-TOG are at the very end of the microtubule, they move ahead of other +TIPs like “end-binding proteins”, e.g. EB3.
What is the function of TACC3 as a +TIP?
We think that TACC3 is piggybacking on ch-TOG while it is acting as a polymerase, but any biological function or consequence of this piggybacking was difficult to detect. We couldn’t see any clear effect on microtubule dynamics when we removed or overexpressed TACC3. We did find that loss of TACC3 affects how cells migrate, but this is not likely to be due to a change in microtubule dynamics.
I thought TACC3 and ch-TOG were centrosomal proteins…
In the paper we look again at this and find that there are different pools of TACC3, ch-TOG and clathrin (alone and in combination) and describe how they reside in different places in the cell. Although ch-TOG is clearly at centrosomes, we don’t find TACC3 at centrosomes, although it is on microtubules that cluster near the centrosomes at the spindle pole. TACC3 is often described as a centrosomal protein in lots of other papers, but this is quite misleading.
We were on the cover – whatever that means in the digital age! We imaged a cell expressing tagged EB3 proteins, EB3 is another +TIP. We coloured consecutive frames different colours and the result looked pretty striking. Biology Open picked it as their cover, which we were really pleased about. Our paper is AOP at the moment and so hopefully they won’t change their mind by the time it appears in the next issue.
This is the second paper that we have deposited as a preprint at bioRxiv (not counting a third paper that we preprinted after it was accepted). I was keen to preprint this particular paper because we became aware that two other groups had similar results following a meeting last summer. Strangely, a week or so after preprinting and submitting to a journal, a paper from a completely different group appeared with a very similar finding! We’d been “scooped”. They had found that the Xenopus homologue of TACC3 was a +TIP in retinal neuronal cultures. The other group had clearly beaten us to it, having submitted their paper some time before our preprint. The reviewers of our paper complained that our data was no longer novel and our paper was rejected. This was annoying because there were lots of novel findings in our paper that weren’t in theirs (and vice versa). The reviewers did make some other constructive suggestions that we incorporated into the manuscript. We updated our preprint and then submitted to Biology Open. One advantage of the preprinting process is that the changes we made can be seen by all. Biology Open were great and took a decision based on our comments from the other journal and the changes we had made in response to them. Their decision to provisionally accept the paper was made in four days. Like our last experience publishing in Biology Open, it was very positive.
Gutiérrez-Caballero, C., Burgess, S.G., Bayliss, R. & Royle, S.J. (2015) TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation. Biol. Open doi:10.1242/bio.201410843.
Nwagbara, B. U., Faris, A. E., Bearce, E. A., Erdogan, B., Ebbert, P. T., Evans, M. F., Rutherford, E. L., Enzenbacher, T. B. and Lowery, L. A. (2014) TACC3 is a microtubule plus end-tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types. Mol. Biol. Cell 25, 3350-3362.
The post title is taken from the last track on The Orb’s U.F.Orb album.
This post is about a paper that was recently published. It was the result of a nice collaboration between me and Francisco López-Murcia and Artur Llobet in Barcelona.
The paper in a nutshell
The availability of clathrin sets a limit for presynaptic function
Clathrin is a three legged protein that forms a cage around membranes during endoctosis. One site of intense clathrin-mediated endocytosis (CME) is the presynaptic terminal. Here, synaptic vesicles need to be recaptured after fusion and CME is the main route of retrieval. Clathrin is highly abundant in all cells and it is generally thought of as limitless for the formation of multiple clathrin-coated structures. Is this really true? In a neuron where there is a lot of endocytic activity, maybe the limits are tested?
It is known that strong stimulation of neurons causes synaptic depression – a form of reversible synaptic plasticity where the neuron can only evoke a weak postsynaptic response afterwards. Is depression a vesicle supply problem?
What did we find?
We showed that clathrin availability drops during stimulation that evokes depression. The drop in availability is due to clathrin forming vesicles and moving away from the synapse. We mimicked this by RNAi, dropping the clathrin levels and looking at synaptic responses. We found that when the clathrin levels drop, synaptic responses become very small. We noticed that fewer vesicles are able to be formed and those that do form are smaller. Interestingly, the amount of neurotransmitter (acetylcholine) in the vesicles was much less than the volume of the vesicles as measured by electron microscopy. This suggests there is an additional sorting problem in cells with lower clathrin levels.
A third reviewer was called in (due to a split decision between Reviewers 1 and 2). He/she asked a killer question: all of our data could be due to an off-target effect of RNAi, could we do a rescue experiment? We spent many weeks to get the rescue experiment to work, but a second viral infection was too much for the cells and engineering a virus to express clathrin was very difficult. The referee also said: if clathrin levels set a limit for synaptic function, why don’t you just express more clathrin? Well, we would if we could! But this gave us an idea… why don’t we just put clathrin in the pipette and let it diffuse out to the synapses and rescue the RNAi phenotype over time? We did it – and to our surprise – it worked! The neurons went from an inhibited state to wild-type function in about 20 min. We then realised we could use the same method on normal neurons to boost clathrin levels at the synapse and protect against synaptic depression. This also worked! These killer experiments were a great addition to the paper and are a good example of peer review improving the paper.
Fran and Artur did almost all the experimental work. I did a bit of molecular biology and clathrin purification. Artur and I wrote the paper and put the figures together – lots of skype and dropbox activity.
Artur is a physiologist and his lab like to tackle problems that are experimentally very challenging – work that my lab wouldn’t dare to do – he’s the perfect collaborator. I have known Artur for years. We were postdocs in the same lab at the LMB in the early 2000s. We tried a collaborative project to inhibit dynamin function in adrenal chromaffin cells at that time, but it didn’t work out. We have stayed in touch and this is our first paper together. The situation in Spain for scientific research is currently very bad and it deteriorated while the project was ongoing. This has been very sad to hear about, but fortunately we were able to finish this project and we hope to work together more in the future.
We were on the cover!
Now the scientific literature is online, this doesn’t mean so much anymore, but they picked our picture for the cover. It is a single cell microculture expressing GFP that was stained for synaptic markers and clathrin. I changed the channels around for artistic effect.
J Neurosci is slightly different to other journals that I’ve published in recently (my only other J Neurosci paper was published in 2002). For the following reasons:
- No supplementary information. The journal did away with this years ago to re-introduce some sanity in the peer review process. This didn’t affect our paper very much. We had a movie of clathrin movement that would have gone into the SI at another journal, but we simply removed it here.
- ORCIDs for authors are published with the paper. This gives the reader access to all your professional information and distinguishes authors with similar names. I think this is a good idea.
- Submission fee. All manuscripts are subject to a submission fee. I believe this is to defray the costs of editorial work. I think this makes sense, although I’m not sure how I would feel if our paper had been rejected.
López-Murcia, F.J., Royle, S.J. & Llobet, A. (2014) Presynaptic clathrin levels are a limiting factor for synaptic transmission J. Neurosci., 34: 8618-8629. doi: 10.1523/JNEUROSCI.5081-13.2014
The post title is taken from “Outer Limits” a 7″ Single by Sleep ∞ Over released in 2010.