They grow up so fast – Durham cytoskeleton meeting

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Conro presenting his poster on intron retention; yes, he spelt his name wrong on the poster!  

Yesterday MRes students Liam and Conro attended “Scaling, the cytoskeleton and mechanobiology” at the University of Durham. Courtesy of help with printing from Prof Roy Quinlan, Conro was able to present his recent MRes project data about using a minigene construct to study splicing regulation in LAMA3.

I was on holiday so unable to attend so asked the guys to take  pictures. In response I not only received the obligatory “proud student presenting his work” image but also some token tourist shots of Durham and slides from the talks.

Looks like an interesting meeting and sad to have missed it!

Also, according to Conro, “hagfish are cool”

 

St Paul’s Eye Appeal fundraising dinner

Last week St Paul’s eye unit and the Department of Eye and Vision Science at the University of Liverpool hosted a dinner at Liverpool town hall to promote the St Paul’s Eye Appeal. This appeal supports a number of research projects that don’t fit into the common funding mechanisms. i.e. the appeals fills the gap between the research supported by the big research councils and the clinical services supported by the NHS.

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Liverpool Town Hall 

In practical terms it makes a massive difference to our department; allowing for strategic investment in people, projects and equipment to push forward new research ideas and get them into the clinic.

It was a great night with a fantastic locally sourced food,

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The £1 million dining table, no drink rings please!

wine and gin and really good company. Lots of valuable connections were made and hopefully this will translate into investments into eye research in Liverpool.

The dinner was hosted by Lady Grantchester and amongst the other notable dignitaries  was Stephanie Slater MBE, the paralympic athlete who recently had a corneal transplant at St Paul’s. Not my usual company (!) but a really interesting experience for all involved.

Here are a few photos from the night and select ones involving some of the EVS team below.

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Eye eye eye?

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Putting together the images from our sunscreen project to prepare the manuscript…. Here are a bunch of the eye images that MRes student Kareem took.

Not sure why but I find it strangely compelling so thought I would share. If you were part of the study I challenge you to spot yourself…

Can’t wait for the paper? The abstract was selected for oral presentation at the British Association of Dermatologists meeting in June, so you will be able to see Kareem in action there.

Lung Fibrosis Studentship Available in Hamill lab

We are pleased to announce we have been awarded funding do a really cool project in the area of matrix assembly in the alveolar epithelium and are currently accepting applications for a funded PhD studentship position. Interested? apply here;

Determination of the mechanisms through which age and disease associated alveolar epithelial matrix changes drive development and progression of pulmonary fibrosis.

Pulmonary fibrosis is a major clinical problem with massive financial and morbidity implications. Importantly, once a fibrotic extracellular matrix (ECM) is formed it currently cannot be reversed, moreover, disease progression continues with the fibrotic matrix shown to induce further profibrotic responses and even exposure to “old” ECM is sufficient to drive changes to matrix protein production and increase the risk of developing pulmonary fibrosis.

Unlike many other matrices, the alveolar ECM is exposed to stretch, with forces increasing. Accumulating evidence point to a critical role for the alveolar basement membrane (BM) in stretch responses, specifically to the importance of laminins (LM) in normal and pathological lung function. It has been shown that LMα 3 expression decreases with and is frequently lost in patients with pulmonary fibrosis, while other LMs expression is dysregulated in scleroderma associated lung fibrosis. Alveolar epithelial cell (AEC) LMα 3 knockout animals display increased fibrosis and mortality in the bleomycin fibrotic but is against overextension in ventilator induced lung injury models. Interestingly, whereas LMs are organized in cloud like arrays in matrix of skin/corneal epithelial cells, in AECs they assembles into fibrillar arrays (figure) and LMα 3 has been shown to stretch signal via a complex containing nidogen, perlecan, and dystroglycan.

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Laminin network assembly responds to stretch. Left; skin epithelial cells, Right; alveolar epithelial cells exposed to cyclic stretch, both stained with antibodies against laminin alpha3 (Hamill et al. JCS 2009)

However, surprisingly little is known about how alveolar epithelial cells assemble their BM; how the LM assembles differently under stretch, the effect on other BM components of changing the LM matrix, the effect of age-associated changes to the ECM and how those changes lead to fibrosis susceptibility is yet to be investigated. This studentship will use in vitro models and scleroderma patient samples to answer these questions.

To answer these questions this studentship will use in vitro stretch models of alveolar epithelial cells in 2D and 3D culture along with pulmonary fibroblasts along with a variety of cell and molecular approaches. These will include high end techniques such as mass spectroscopy, genome editing, and live cell/molecular imaging modalities including superresolution microscopy and atomic force microscopy.

The student undertaking these studies will benefit from a diverse supervisory team each bringing valuable skills to the project. The studentship will take place primarily in the custom built laboratories of the Institute of Ageing and Chronic Disease at the University which opened in 2016. You will also join a team of scientists investigating different questions relating to pulmonary fibrosis and stretch signalling.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

 

At minimum applicants should hold or expect to obtain a 1st class or upper second class undergraduate degree or a masters level qualification within biochemistry, molecular or cellular biology disciplines or related fields. Preference will be given to students with extensive lab experience.

Want to know more about the lab/institute:

Lab website: https://spark.adobe.com/page/mXI8W/

Institute Website: https://www.liv.ac.uk/ageing-and-chronic-disease

Funding Notes

This is a funded studentship supported by an endowment to the University of Liverpool. This will provide a stipend, fees at the UK/EU rate and a consumables budget

References

Laminin deposition in the extracellular matrix: a complex picture emerges.
Hamill KJ, Kligys K, Hopkinson SB, Jones JC.
J Cell Sci. 2009 Dec 15;122(Pt 24):4409-17. doi: 10.1242/jcs.041095.

Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.
Morales-Nebreda LI, Rogel MR, Eisenberg JL, Hamill KJ, Soberanes S, Nigdelioglu R, Chi M, Cho T, Radigan KA, Ridge KM, Misharin AV, Woychek A, Hopkinson S, Perlman H, Mutlu GM, Pardo A, Selman M, Jones JC, Budinger GR.
Am J Respir Cell Mol Biol. 2015 Apr;52(4):503-12. doi: 10.1165/rcmb.2014-0057OC.

Lung-specific loss of the laminin α3 subunit confers resistance to mechanical injury.
Urich D, Eisenberg JL, Hamill KJ, Takawira D, Chiarella SE, Soberanes S, Gonzalez A, Koentgen F, Manghi T, Hopkinson SB, Misharin AV, Perlman H, Mutlu GM, Budinger GR, Jones JC.
J Cell Sci. 2011 Sep 1;124(Pt 17):2927-37. doi: 10.1242/jcs.080911.

 

https://www.findaphd.com/search/projectDetails.aspx?PJID=83871

Burns Night

Last night the Hamill team celebrated the life and works of Robert Burns with a night of food, poetry, song and dance with team members, partners, children and friends. It was a fantastic time with much hilarity, delicious food and drink. Many thanks to everyone for coming and for making it such a fun night.

Unfortunately I forgot to the get the camera out ’til later in the evening so missed Valentina’s address to the laddies, Lee’s address to the Lassies (including his primary school poetry!), the haggis (and related shock on many faces in finding out it is fantastic!). Trust me though they were all great!

Its long overdue that we had a team gathering; events like these really cement that I have assembled a fantastic team and am looking forward to a fun and productive times together.

What we were able to capture for posterity was MRes students Kareem, Tobi and Conor displaying a distinct lack of ability at beer pong and, in particular, Tobi’s inimitable technique!

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They grow up so fast – MRes 2016-17 project 1

New year, new poster session with Hamill lab students in action. This time its the turn of two MRes students from this year’s clinical sciences cohort.

Tobi Oyewole’s project looked into changes in LaNt a31 distribution in corneal limbal explants, a model of corneal wound repair in relation to proteins associated with of limbal basal epithelium/wound repair. He generated some pretty nice histology images working closely with Dr Valentina Barrera20170113_130648 including a bunch of images that quite nicely showed that our old rabbit pAb LaNt and new mouse mAb recognise very similar distributions (quite a relief really). Tobi’s work was presented at Mercia Stem Cell conference recently and Vale is continuing on with it and hopefully it will contribute to a manuscript later this year.

Kareem Hassanin did a very different project; he investigated issues with sunscre20170113_131709en application behaviour. Compared with my usual Molecular/Cell Biology/Genetics/histology type projects this was a totally different project (lots of fun) that we decided to do after a few conversations with one of my clinical colleagues (Austin McCormick) an eyelid cancer specialist. It also brought in Harry Pratt and Yalin Zheng as image analysis specialists and Gabriella Czanner as a statistician which has meant this really simple study has generated some really robust data. Conference abstract has
been submitted and the manuscript being prepared for submission very soon. 20161102_151712

The recruitment poster he used for to assemble the cohort could equally well have doubled as a wanted poster for myself (and was modified such in some of the communal areas….) and it was stated today that the people institute were pleased to no longer have my face staring at them every morning!

I also now have a big collection of comedy photos from most of the students and postdocs in the institute and have cool UV camera that we will be using in public engagement events this summer.

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They grow up so fast – Mapstone prize winner edition

Congratulations to PhD student Karen Lester on a prize winning talk at the Department of Eye and Vision Science and St Paul’s Eye Unit annual ophthalmology presentations.

Karen’s studies are trying reverse engineering glaucoma in order to identify new therapeutic targets to treat this blinding disease. She already has some interesting findings and its developing into really nice story. Her studies are under the primary direction of Prof Colin Willoughby with input from  Drs Carl Sheridan, Anshoo Choudray and myself.

Interested in her work? You can see it presented at Asia ARVO in February and hopefully in print sometime soon!

Lab medals?

medalsYesterday we had the pleasure of welcoming Paraolympic athlete Stephanie Slater to our lab. Stephanie won gold (4×100 medley relay) and silver (100m butterfly) in Rio 2016 as well as gold and silvers at the 2013 world championships. Stephanie has suffered from a rare ocular disorder called Keratoconus (cone shaped cornea) that leads to bulging out of the front of the eye which distorts vision and, as the disease worsens with age, ultimately leads to blindness. However, Stephanie recently received a corneal transplant from the surgeons at St Paul’s Eye Unit in Liverpool hospital.

Her visit to the lab was to promote her story and, in so doing, promote eye donation. Cornea transplantation is the most successful transplantation surgery but there is a critical shortage of donor material available and that leads to many people waiting for extended periods of time before getting access to treatment.

The story was picked up by a bunch of news sources and featured on BBC’s Northwest tonight (12m 39s in to this http://bbc.in/2hK6Tpw only available for a couple of days) and also featured a few B-roll and background shots of my colleagues demonstrating eye related research including eye dissection.

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The story could have been wholly focused on the clinical aspects so it was really appreciated that they decided to include the value of research aspects. Our work in Eye and Vision Science at Liverpool uses, and in many ways relies on, access to donor eyes that are unsuitable for transplantation and also the “extra” bits that don’t get used (for example, in my lab,  after the central cornea is used in transplant we use the surrounding rim of tissue in our studies as a model of wound healing and stem cell activation). These are a rare resource and not available to all researchers and it really makes research at Liverpool stand out. It should also be pointed out that many of the current treatments were first tested in lab settings and the improvements in the future and all the new treatments that will be developed will come from the fundamental research being carried out just now in research institutes like ours .

As part of her visit Stephanie and her mum had a tour of our facilities and I got a chance to show some cool live imaging experiments (of course the photographer captured the point where I was showing laminin deposition, I did show other stuff too!). I was also able to show images from research that Shao-Hsuan Chang (a PhD student supervised by Prof Colin Willoughby, Ahmed Elsheikh and myself) generated where she is looking at the efficacy of keratoconus treatments. It’s always really rewarding being able to show the progress you are making toward either the understanding of a patient’s condition or the steps that are being taken toward a new treatment. It’s also really good to hear directly from the patients themselves where the problems lie, this helps direct our short term research goals.

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Also super cool was getting to handle the medals. Pretty much everyone wanted to pose with them. Here is PhD student Lee Troughton who works on wound repair and claims that this gold medal was awarded for being  “top, top scientist” (his words, and will likely appear on his CV)

15697707_10154040464112073_1735871806883474445_nand below, Karen Lester who is investigating new therapeutic targets for glaucoma. She is a lot more self aware!

“Meet an Olympian ✔
Steal gold medal ✔
Feel completely inadequate ✔
What an inspiration. Some woman for one woman!”

 

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You can read other press releases from the hospital  here, and university here

 

They grow up so fast – 3rd year tutorial group edition

Busy couple of weeks with the semester ending and various groups of my students being tasked to create a poster. Yesterday was the turn of my 3rd Molecular Biology students who chose to look at miRNA and age-related disease.

They did a thoroughly good job, without really needing any input from me. I don’t know who “won” in the day but I certainly thought that my team were up there with the best; unlike some of the others which were broad and superficial they went deep enough that everyone who spoke with them could learn something.20161214_143340

They grow up so fast; Mercia stem cell alliance conference edition.


Dr Valentina Barrera and MRes student Tobi Oyewole were in action today, presenting the work from the last few months at the Mercia Stem Cell Alliance conference. Unfortunately couldn’t make it so Vale got the opportunity to act as the proud parent to the first time presenter.