It’s from the comfort of my living room sofa that I write my final blog for 2022, cup of tea in hand and a purring cat on my lap as I tap away on my keyboard. This month, to round up 2022, I have decided to blog about what I have achieved – and not achieved – this year, as I reflect back on another year of my science and what – hopefully exiting stuff – 2023 could bring.
I have always struggled with giving myself time and space to take a step back and take stock on what I have achieved, in the past week, month or year – possibly because I always tend to magnify all the negatives and brush over the positives. It’s uncomfortable right? When you come face to face with the reality that everything on the to do list has not been ticked off. And why do we dismiss what has been ticked off so easily?
For example, I am at a stage in my career where I am starting to – seriously – think about applying for a fellowship after I finish my postdoc. And what are two things that are very important when applying for a fellowship? Bar having a good idea of course, 1) publish papers and 2) track record of securing funding. Both of which I did zero of this year – piling on the pressure. But what I have done this year, which is not so easily put pen to paper and ticked off a list, is meeting and talking to other researchers within and outwith my institution. It’s too early to know if any of these meetings will spark any collaborations in future but new interactions facilitate new ideas, new hypotheses which in turn generate grant applications and hopefully publications. So, on reflection – as this is the theme – I am laying down the groundwork and with a wee bit of patience I hope to reap the benefits.
Related to not publishing any papers, and something new I have had to grapple with this year, as I transitioned into my second postdoc, is finishing up outstanding work and manuscript writing from my previous post. Which again, I have achieved very little, if not nothing of. This topic most definitely merits a stand-alone blog post, but for now let’s just say that, trying to keep in touch with previous collaborators and abreast of new discoveries in a different field from the one I am currently working in, alongside doing the research I am actually paid to do, can feel overwhelming at best and at worst, impossible. Momentum grinds to a halt and motivation dwindles, especially when you are no longer the person driving that work. So, on reflection – you know where this is going by now – I haven’t managed to publish that paper from my previous postdoc but what I have done, which again is much less tangible and measurable, is settling in and finding my feet in my new lab. This led to getting a surgical technique set up and running again, supervising an intercalating vet student, rederiving and establishing a mouse line that will be essential for my postdoc moving forward, organising ECR events within the Edinburgh DRI as well as across other DRI centres and most recently co-line managing a research assistant.
2022 has also brought two new experiences, which most definitely were not on my to do list. I was asked to peer-review my first manuscript and from then on approached by multiple journals within my readership to review other manuscripts for them. I also had the opportunity to be involved in other projects within and outwith my lab, which are all incredibly exciting. Both examples, have different challenges and give new meaning to the words prioritisation and time-management. And don’t be fooled – I’m still trying to navigate how to keep propping up the numerous spinning plates academia keeps pilling on. But what I have concluded from this, is that my expertise in the field is starting to be recognised, both by my immediate research network and the broader science community.
And finally, what I am most looking forward to getting stuck-in in 2023? Drum roll please, is to properly kick off my postdoc project! Yep, you have read that right. It’s been in the works for such a long time, I almost don’t want to jinx it. Bear with me as I set the scene…
We already know, that the innate immune response occurs in three phases following ischemic injury and is driven by resident microglia and infiltrating monocyte-derived macrophages (MDMs). We also know that aberrant, overly robust or prolonged inflammation can lead to chronic maladaptive neuroimmune responses impeding recovery and, in some cases, leading to post-stroke cognitive decline. What we still don’t fully understand is the specific cell types active at each stage, their roles in tissue repair and their interactions with the wider neurovascular unit. These are all critical pieces of the puzzle to enable the development of immune-based therapies mitigating secondary injury and preventing cognitive decline.
As an added challenge, once in the brain, MDMs express the same canonical markers as resident microglia, making them indistinguishable from each other. As such, we haven’t been able to precisely pinpoint the contribution of resident vs infiltrating immune cells to stroke outcome thus far. But, in 2019 a study published in Cell [1] identified, with the use of single cell analysis, a specific gene, known as Ms4a3, which is ubiquitously expressed by granulocyte-monocyte progenitors, and not found in resident brain macrophages i.e microglia. With this technique all cells expressing the Ms4a3 gene as well as their progeny will fluoresce (upon CRE recombination with a reporter strain) and all cells that don’t express the Ms4a3 gene won’t. The use of this technique, known as fate-mapping, is revolutionary, as for the first time, we will be able to unambiguously map and discern the individual contribution of resident and infiltrating immune cells to stroke pathology and cognitive recovery both acutely and chronically.
Hopefully I haven’t managed to hijacked the blog to make it ‘all about the science’ – there is plenty of time for that next year! So, I will leave you with a final thought. We are all our worse critic – I think, this especially rings true to all researchers out there – so for 2023 – take it as a New Year’s resolution if that’s your jam – I challenge you, to be kinder with yourself and to not brush over the positives.
Dr Gaia Brezzo
Author
Dr Gaia Brezzo [2]is a Research Fellow based within the UK Dementia Research Institute at The University of Edinburgh. Gaia’s research focuses on understanding how immune alterations triggered by stroke shape chronic maladaptive neuroimmune responses that lead to post-stroke cognitive decline and vascular dementia. Raised in Italy, Gaia came to the UK to complete her undergraduate degree, and thankfully, stuck around. Gaia writes about her work and career challenges, when not biking her way up and down hills in Edinburgh.