Life in the Laminin Lab #5 – Examples

 

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Check back on Monday for #6

#4 available here (and links to the rest) or Meet the characters

Or, if you are feeling really keen, read about how Kevin actually did bring in the Mongol invasion of India in his PhD thesis and viva; here.

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Adding width to a discussion section…. How to include Mongol invasions in your molecular biology PhD thesis!

In the writing guide section of this blog there is a page about writing discussions. On that page, I refer to the concept of adding width to your discussion in a PhD thesis and mentioned that I ended up talking about the invasion of India by the Mongols in my PhD thesis (“Laminin alpha3 isoforms in cutaneous biology and genetic skin disease”).

Some people have since asked how I managed to work that in while still staying relevant. So, for your enjoyment, and because we never published this part of the story, I have copied it below. Enjoy.

Linkage analysis of the LOCS patients revealed the majority of the patients to share a common haplotype around the LAMA3 locus, which strongly suggests inheritance of a common founder mutation. Determination of the age of the mutation itself is not directly possible however using a likelihood based approach the age of the allele, and therefore time to most common recent ancestor (TMRCA), can be calculated. Essentially this process is based on determination of the length of shared haplotype between each of the individual members and therefore the interval in which recombination (or allele mutation) has occurred. To fine map the location of these recombination events, additional markers were designed around the LAMA3 locus. Recombination rates per generation for many markers have been calculated and assembled into genetic maps.

The locations for the newly developed markers were calculated based on their physical location between the two closest known markers. Marker mutation rates and allele frequencies within the same ethnic group were also taken into account and gave a final value of ~500 years with a mutation rate of 1.2 x 10-3 mutations/marker/generation (Weber and Wong, 1993). However mutation rates at each individual marker are different and the average rate quoted by Weber may only relate to more commonly mutated, and therefore more useful, markers. Reducing the mutation rate to a more conservative 1 x 10-4 mutations per marker per generation gives a TMRCA of ~600 years (95%CI 400-900). Confidence intervals are necessarily large due to the large number of variables, however, these calculations do provide a measure of relatedness for the families.

The finding that the LOCS mutation has a population carrier frequency of approximately 1 in 100 in the British Punjabi Muslim population makes it tempting to search for a historical event that may have caused a bottleneck in this population, allowing this allele to reach this relatively high level. The populations of India and Pakistan have historically been divided into subpopulations by barriers of geography, language, religion, caste or biraderi (patrilineage), resulting in the generation of multiple genetic isolates and the LOCS syndrome may reflect one such isolate (Bittles et al., 2004; Wang et al., 2000).

An answer from history would be purely speculative, however, there are major events that may explain the expansion of LOCS haplotype. Invasion by Mohammed of Ghor in 1192, brought north India under Muslim rule and mass conversion from Hinduism to the Muslim faith. In 1397, the Mongols under Timur Lang (Tamerlane) invaded the Punjab region and northern India and ravaged the entire region causing the fragmentation of Islamic India and separation from a wider kingdom to individual, isolated, regional control (http://www.interknowledge.com/india/india02.htm: A concise history of India). As part of this invasion, Lahore was sacked by an army commanded by Iskender, Tamerlane’s son. It is possible that the survivors of this devastation may have included the founder of the LOCS haplotype allowing its expansion within a resultant subpopulation. The timing of this Mongol invasion falls nicely into the window suggested by our TMRCA studies. A further conquest in 1526-7 by the Mongol Babur may again have led to a local reduction in population, which through maintenance by social construction, may have increased the LOCS haplotype carrier number.

The identification of the LOCS mutation may have important ramifications with respect to prenatal screening and genetic counselling within this community. One important consideration is the prevalence of consanguineous marriages within the population and the relatively high carrier frequency, which together greatly increases the risk of inheriting LOCS.

Note; I think my writing has improved in the 12 years since I wrote this! Certainly, I would edit it today and add a load more primary data references.

Also note; I am not a historian, and make no claims about the veracity of the historical comments!

And one more note… although I would probably do things a bit differently now, I don’t think this is necessarily out of place within my body of work. If I was examining this thesis, I would enjoy exploring these ideas with the student. During my viva, the three examiners and I had a solid scientific and entertaining chat about this stuff, a few laughs at the change in style, and genuinely my memories of my viva are positive.

Want to know more about laminins? I wrote a lay person summary awhile back; available here.

Interested in LOCS – (laryngo onycho cutaneous syndrome, sometimes known as LOGIC or Shabbir syndrome? The primary data with some of the linkage data that set up this section is here or patients/non geneticists might prefer the NIH site on this genetic disease.

Life in the Laminin Lab #2 -Poster Prep

poster time

 

Miss #1? find it here.

Hi readers, this is #2 of a new series of cartoons inspired by real events in the Hamill lab. It’s a new thing, it might not work, but they’ve been fun to make and have amused me and the team! So, here you are, #2.

To be fair to the most recent cohort of MRes students, they did a really good job with their posters; two of our team winning prizes. Blog post about them here.

3 more coming this week and we’ll revert to weekly thereafter.

For now, you can also meet the characters or check out some of the other stuff about our lab and research; learn about laminins, read one of the manuscript, thesis, dissertation, or project writing guides for scientific results, or discussion  (intros and methods coming soon) or the lab website

Life in the Laminin Lab #1 – Type I vs Type II error

type I and type II error

#2 available here

Hi readers, this is the first of a new series of cartoons inspired by real events in the Hamill lab. It’s a new thing, it might not work, but they’ve been fun to make and have amused me and the team! So, here you are, #1. 4 more this week and we’ll revert to weekly thereafter.

For now, you can meet the characters or check out some of the other stuff about our lab and research; learn about laminins, read one of the manuscript, thesis, dissertation, or project writing guides for scientific results, or (the new) discussion guide (intros and methods coming soon) or the lab website

They grow up so fast – MRes Jan 2018 edition

Another new year, another new “They grow up so fast” post. This time its the turn of four MRes Clinical Sciences students that have been with our lab for the past 3 months.

Today, the students were presenting their work at a poster session in the Institute of Ageing and Chronic Disease.

Four projects, all different in topic, direction and approach. My lab meetings have been not only large but also really stimulating. Much coffee required to stay on top of it all.

Lizzy Lourenco

20180112_123035(0)Picked up the next stage of the sunscreen studies we did last year (blog posts here, here and here). Using our UV sensitive camera and automated segmentation and analyses algorithms, Lizzy assessed the application habits of people using SPF moisturisers. Her project got lots of help; Gabriela Czanner for stats and design, Yalin Zheng and Harry Pratt for image analysis, Austin McCormick and myself for overall design and direction and Conro helped train Lizzy to get high quality images. Conro also took the pics in this post…. not sure how good a trainer he really was!).

Going in to this study, we expected less moisturiser to be applied in terms of volume compared to the sunscreens but that the users would be more thorough in terms of the coverage of the eyelids; our previous study showed the eyelids to be frequently missed/avoided with sunscreen. Turns out, we weren’t quite right; moisturiser application was actually even worse than the sunscreens. Intriguing. This leads to an important public health message- moisturisers are better than nothing but you still need eye protection. An abstract from this work is already submitted to the big dermatology meeting and we’ll write up the manuscript soon.

EDIT: Lizzy won joint second prize for her poster!

Laura Bowker

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Laura

Laura picked one of our molecular biology projects and worked with Thanos Papadimitropolous on part of his PhD project looking at an RNA therapeutic for a rare eye disorder called aniridia.

I think its fair to say that Laura experienced the full rollercoaster of emotions that accompanies most hypothesis testing scientific research; hope in the early periods, confusion as things don’t work, despair as the time ticks down and finally something close to joy (or perhaps just relief) as the final experiments finally start to deliver data.

Of course, at that point she had to stop. Genuinely, her poster and project write up changed in the last week from “this idea doesn’t work” to “actually, it’s got a chance”

EDIT: Laura won joint second prize with her poster!

Nikitha Pasunu

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Nikitha

Nikitha worked on one of our laminin projects, looking see if we can influence a “splicing switch” that some of our other work suggests goes wrong in squamous cell carcinoma. She worked with the help and guidance of two current PhD students and former MResers Conro Conro Sugden and Liam Shaw in trying to use an RNA approach to flip the switch back again.

Like Laura, Nikitha picked up a project early on its development and so a lot of her time was establishing the model, testing ranges of concentrations and timepoints. To be fair, this is what most time in the lab is spent doing so these 10 week projects are probably a fair reflection of that. Nikitha also ended up with some promising looking results that need lots of further confirmation but could be cool if they keep going the same way. This work will continue thanks to support from North West Cancer Research with Lee Troughton working on the project.

Elizabeth Attree

img_0566Lizzie #2 worked on a project with Dr Valentina Barrera that harks back to Vale’s time before the Hamill lab where she worked on Malarial Retinopathy in Malawian children. In this project Lizzie used immunohistochemistry and histological stains to investigate if and how a range of changes to vessels in the retina can predict disease severity, using the retina as a window to the brain. As always with Valentina involved, lots of really nice images of tissue staining were gathered and it turned into a well developed project.

It’s been fun, productive and hopefully enlightening for the students.

 

poster day

Coming soon… “Life in the Laminin Lab”

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I know many of you will have been thinking  “there just aren’t enough comics about all the mildly amusing things that happen in a lab”. Well, good news! As I was illustrating my recent posts about writing (results, discussion) I ended up with a character that bore a passing resemblance to myself (I was aiming for generic professorial type!). Those cartoons were pretty rubbish so I updated them a bit and suddenly we have a cast of characters. Yes, I appreciate that they are still rubbish.

With a cast, all we need is material…. luckily for that bit we have all the entertaining things Liam, Thanos, JohnJohn, Conro et al get up to. If you have an interesting lab-related story (especially if you work in IACD) let me know and we’ll add it to the list.

So, stay tuned. We’re aiming to make this a regular feature, starting soon.

And yes, laminin jokes are a thing.

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New content; Results writing guide

A how to guide for writing results sections for scientific reports / manuscripts / PhD thesis chapters has been added to the pages section of this blog. In it you will find some of my thoughts on how you can maximise the effectiveness of your results subsection and hopefully make people enjoy reading your work! It’s aimed at PhD students, MRes or undergraduate project students but might also be useful for anyone teaching this sort of material.

Over the past week we ran a series of workshops aimed at helping students and postdocs with elements of their scientific writing – if you want the ppt files that went with these sessions let me know.  The people attending really seemed to appreciate the week and I thought that this content could be useful.

Have a look, see what you think, comments are appreciated (as always).

If this sort of content is any use, I will write up some of the other talks I prepared for the other parts of theses / manuscripts.

I’m aware that there are lots of similar content on the web already, so I’ve tried to go a bit deeper into the thought processes in mine to try and help readers develop their skills. If you are looking for something much simpler, I wrote a quick blog post awhile back. The blog post is a lot more proscriptive and less developed but could be useful if you are in a rush!

Types of results subsection

New content; introduction to laminins

I’ve added a “non-scientist”-friendly introduction to laminins to the site today. Kinda wikipedia-like but with more connection to what we work on. If you have 5 mins, can you have a look via the link above and provide a bit of feedback about whether I have managed to write this in a way that works to effectively introduce this protein family in an accessible way.