Author Archives: Sarah Robinson

Words of Wisdom from final year PhD students

NB: These are entirely subjective so please ignore them all if you want.

1.     Write everything down in a searchable place 

Maybe you are gifted with a brilliant memory but, for the rest of us, write everything down (either in a notebook, or better yet, some kind of searchable typed document). This includes notes from supervisor meetings, industry meetings, clever suggestions over coffee, group meetings, etc… 

In our experience, writing things on paper is risky unless you have a decent filing system (see our desks for examples of how not to file notes). It also requires writing legibly. Typed notes are also particularly useful for saving common error messages/bug fixes/useful installation instructions/functions etc in one place so that you can easily search for them again! This can be just a word document, o rGemma showed me “Notion” which has so far been really useful (and you get to put emojis next to your notes).

This also leads to the second tip…

2.     Type up notes on papers you’ve read or use a reference manager 

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AIRR Community Meeting VI May 17-19 

Eve, Brennan and I were delighted to attend the sixth AIRR (adaptive immune receptor repertoire) Community Meeting: Exploring New Frontiers in San Diego. Eve and I had been awaiting this meeting for a mere 3 years, since it was announced during the last in-person AIRR Community Meeting back in 2019. Fortunately, San Diego did not disappoint. 

After a rocky start (featuring many hours stuck in traffic on the M40, one missed flight and one delayed flight), we made it to California! The three day conference had ~230 participants (remote and in-person) and featured great talks from academia and industry. We particularly enjoyed keynote talks from Dennis Burton on rational vaccine design using broadly neutralising antibodies, Gunilla Karlsson Hedestam on functional consequences of allelic variation, Shane Crotty on covid and HIV vaccine design, and Atul Butte on uses of electronic health record data and how we should all found start-ups.

We had fun delivering a tutorial on OPIG antibody tools and, most importantly, we all won AIRR t-shirts in the raffle (potentially we were the only people who noticed how to enter on the conference app). Highlights outside of the conference included paddle boarding and seeing hummingbirds, pelicans, sealions, seals, ‘Garibaldi’ the state fish, and meeting Bob the golden retriever at a surfing shop. We’re now off to find jobs on the West Coast so we can live at the beach….

 The AIRR community has many webinars and talks available on their youtube channel https://www.youtube.com/c/AIRRCommunity

Sarah, Eve & Brennan

What is a plantibody?

Plants can be genetically engineered to express non-native proteins, for example, crops can be engineered to produce insect toxins in order to improve disease-resistance. However, I was not aware of their ability to express antibodies until, inspired by my expanding collection of house plants, I googled ‘plant immune systems’. 

Plants don’t naturally produce antibodies – they do not possess an adaptive immune system or any circulating immune defence cells. Despite this, plants can be made to express and assemble full length antibody heavy chains and light chains. This was first published back in 1989, when Hiatt et al. [1] successfully introduced mouse immunoglobulin genes to tobacco plants and produced functional antibodies with reasonable efficiency. The excellent term ‘plantibody‘ was coined soon after, to refer to antibodies and fragments of antibodies produced by plants transformed with antibody-coding genes. 

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Antibody Engineering and Therapeutics Conference

I was invited to speak at the Antibody Engineering and Therapeutics Conference (presenting mine and Matt’s recently published epitope profiling paper), in San Diego (December 12th – 16th). Unfortunately, the pandemic had other ideas so I decided not to travel but luckily the conference was hybrid. 

The conference included 1 day of pre-conference workshops and 4 days of presentations from academic and industry, with livestreaming of the initial keynotes (including one from Charlotte). Remaining talks were recorded and made available after the conference. I’ve highlighted a few of my favourite talks and conference themes, with links to papers where available.

Naturally, a lot of the presented research related to covid-19. I was speaking in the ‘Antibody Repertoires and Covid-19’ session, where there were interesting presentations from Professor Eline Luning Prak from the University of Pennsylvania and Elaine Chen from Vanderbilt University analysing antibody responses in covid-recovered individuals, and comparing vaccine responses in covid-recovered vs covid-naiive individuals. Other talks around SARS-CoV-2 vaccines included Dr Laura Walker from Adimab/Adagio Therapeutics comparing BCR repertoire responses to different types of vaccinations, and the effect of using different booster types.

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Former OPIGlets – where are they now?

Since OPIG began in 2003, 53 students* have managed to escape. But where are these glorious people now? I decided to find out, using my best detective skills (aka LinkedIn, Google and Twitter).

* I’m only including full members who have left the group, as per the former members list on the OPIG website

Where are they?

Firstly, the countries. OPIGlets are mostly still residing in the UK, primarily in the ‘golden triangle’ of London, Oxford and Cambridge. The US comes in second, followed closely by Germany (Note: one former OPIGlet is in Malta, which is too small to be recognised in Geopandas so just imagine it is shown on the world map below)

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Do antibodies care about sex?

In a recent OPIG antibody meeting, the topic of immune system differences between men and women came up. I thought this was cool and something I hadn’t read about, so what a brilliant topic for a blog most. This post is a high-level overview – I’ve listed the papers I’ve used at the bottom of this post so please consult them for more details!

Differences between males and females can lead to pretty big disparities in disease prevalence and outcomes. For example, non-reproductive cancers occur predominantly in males, whilst the majority of autoimmune disease occurs in females. Many factors may be impacting this, including environmental, genetic and hormonal influences, and much more research is required to fully understand these processes. Here I focus on sex-based biology, rather than gender, though both can influence the immune response.

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AIRR Community Meeting V – December 2020

We attended the virtual Adaptive Immune Receptor Repertoire (AIRR) Community Meeting in early December. The three day conference is usually held every 18 months and covered a range of research talks, software demonstrations and poster presentations on the latest TCR and BCR (antibody) research. While we missed certain elements that were present at the last AIRR community meeting (namely focaccia), it was a really interesting meeting with technology all running very smoothly.

Given our current research on SARS-CoV-2 antibodies, we particularly enjoyed the work presented by Armita Nourmohammad from the University of Washington on “Dynamics of BCR in Covid”, based on the preprint on medRxiv. The research identified 34 significantly expanded rare clonal lineages shared among patients with SARS-CoV-2, which are potential candidates for covid response. In particular, the analysis includes an assessment of whether an antibody sequence identified in different individuals (known as a shared or public sequence) is likely to be found due to inherent biases in antibody recombination. Shared antibody sequences which are calculated as  unlikely to be shared are potentially a response to a shared exposure such as SARS-CoV2, rather than randomly found in the antibody repertoire. In this way, Nourmohammed and colleagues identified ‘rare’ antibodies which were identified in more individuals than would statistically be expected, and therefore might be worthy of further experimental analysis.

A theme common across a short talk and poster by Hadas Neuman (Bar-Ilan) and a poster by Kenneth Hoehn (Yale), was class-switching dynamics revealed by phylogenetic inference (from IgM to IgA in the human gut in the former, and IgE and IgG4 in a paediatric patient with peanut allergy in the latter). Kenneth Hoehn’s poster also looked at B-cell differentiation during HIV infection – this can all be read about in this preprint. The methods developed in the paper for discrete trait analysis of differentiation, isotype switching and B-cell migration are implemented in the new R package dowser (https://bitbucket.org/kleinstein/dowser) which is part of the Immcantation suite (http://immcantation.org).

It was also really nice to see evidence of the burgeoning use of single-cell sequencing for immune repertoire profiling, with posters by Igor Snapkov (UiO), Indu Khatri (Leiden University Medical Centre), Nick Borcherding (Washington University in St. Louis) all using single-cell technologies, and a talk by Ivelin Georgiev on LIBRA-seq. 

If you missed the conference and have had your interest piqued, some of the conference talks are available at the AIRRC youtube channel.

We look forward to AIRRC6, Dec 7 – 11, 2021!

Sarah and Eve

Curing Dogs With Cancer: The Power of the Antibody

This blog post finally combines the two great passions of my life: antibodies and dogs. Therapeutic antibody development is a huge area and is certainly not limited to humans. In the process of developing antibodies, we often use mouse or rat antibodies, obtained by injecting the animal with the antigen of choice and then collecting the resulting antibodies. The first monoclonal antibodies (mAbs) were produced in this way, by fusing spleen B cells from an immunised mouse or rabbit with immortalised myeloma cells to form antibody-expressing hybridoma cells. However, using antibodies to treat disease in animals lags behind humans.

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C is for Cysteines (plus a fun quiz)

At group meeting a few weeks ago I presented this paper, “Landscape of Non-canonical Cysteines in Human VH Repertoire Revealed by Immunogenetic Analysis“, from Prabakaran and Chowdhury. The paper is an investigation of the frequency, location and patterns of cysteines contained in human antibody sequences. Cysteines are important amino acids found in proteins, including antibodies, which can form disulphide bonds with other cysteines due to the presence of their reactive sulfhydryl group in the side chain.

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When antibodies go wrong: how antibodies can help viruses infect cells

I’ve been keeping up to date with the latest coronavirus vaccine developments using Derek Lowe’s blog, a resource which I cannot recommend highly enough. A recent post mentioned that vaccines developers are looking out for signs of antibody-dependent enhancement (ADE), which I vaguely remembered from my undergraduate biochemistry days researching an essay on dengue fever. ADE is an interesting immunology phenomenon, and so I thought I’d treat you all to a brief introduction to the issue.

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