In News

We are delighted to see that the latest study on the mechanisms of chemo-resistance in T-cell Acute Lymphoblastic #Leukemia (T-ALL) by Jingliao Zhang and colleagues is now published in the prestigious journal, Blood!

T-ALL is an aggressive cancer not least because of the propagation of resistant cancer clones that drive disease recurrence. Jingliao Zhang et al. (Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College) wanted to dissect the nature of these clones to work out how their presences might contribute to resistance to #chemotherapy .

Combining single cell RNA sequencing with T-cell receptor sequencing of paired diagnosis-relapse T-ALL samples, the researchers identified two leukemic evolutionary patterns: “clonal shift” and “clonal drift”. They additionally saw high expression of the RNA-binding protein MSI2 in the clones persisting at the point of disease relapse. Digging deeper, the researchers conducted functional studies showing that MSI2 contributed to T-ALL proliferation and promoted #chemoresistance through the posttranscriptional regulation of the #oncogene, MYC.

These findings have important implications, as they identify MSI2 as an informative biomarker and novel therapeutic target in T-ALL.

Congratulations to all those involved in this intricate study! For those of you who would like to learn more, the paper can be found online here: https://lnkd.in/dcRJVgr9

In Blog

At the start of the year, we launched our “fresh look” grant editing service. We have already started working with many of you and look forward to learning the outcome of your proposals later in the year. Meanwhile, IEL’s Director and senior editor Dr. Neil McCarthy has put together a three-part blog on “How to write winning grant applications”.

About Neil

Before finding out what Neil has to say in the final part of his blog, let’s find out why he is ideally placed to provide IEL clients with some useful hints and tips on successful grant writing!

Many of you will know Neil as a senior editor with Insight Editing London (IEL), but he is also a Lecturer in Immunology / MRC Career Development Fellow in the Faculty of Medicine at Queen Mary University of London. Neil is Research Lead in The Blizard Institute’s Centre for Immunobiology, as well as Infection and Inflammation Lead in the cross-faculty Centre for Predictive in vitro Models. He has secured more than £1M in personal research funding to date, including research council grants, via charitable sources, and through various commercial projects. Let’s hear what Neil has to say, in part 3 of his blog, “Fellowships: Person – Project – Place“.

 

Fellowships: Person – Project – Place

In the case of fellowships (UK), there is a heavy focus on the individual candidate applying in addition to the standard elements of a conventional project grant. When looking at track record, will the reviewer be convinced that this is the ideal person to deliver a given piece of research? Is the project itself important to conduct, and will this be done in the ideal place to achieve the study goals. Ideally, the experiments will appear exciting and necessary, but difficult to imagine how these could be delivered except by funding this specific individual and their current application. Given the major emphasis on a particular candidate and their expertise, it is often useful to explain how any new skills needed to deliver the project will be obtained by training at second institute. This helps demonstrate that the applicant themselves will also develop and progress alongside their study. As with all project grants, it is vital to convince reviewers that you will be using the best possible techniques to address an important biomedical question. Will the relevant field have moved forward significantly upon completion of this study? Will the funded individual then be in a position to ultimately become a world leader in their field? How likely are the data generated to lead to new technologies / therapies / knowledge in critical areas? These questions are not easily addressed and it will take time to construct a compelling case to tackle each. Which brings us back to the golden rule, that you should always START EARLY!

If you would like to get in touch with Neil to discuss your grant writing projects, please email (early!): neil@insighteditinglondon.com

In News

New insights into physiological and pathological brain wiring

We’re excited to share news of the publication of a fantastic article by an IEL client last month, edited by IEL’s Ilya Demchenko.

Published in PNAS as an open access article, Sinclair-Wilson and colleagues describe their ground-breaking work on the plasticity of brain circuits in neonates, which is important for the correction of embryonic thalamocortical axon mis-targeting. Using a genetic mouse model, the researchers identified a serotonin-dependent window in the immediate post-natal period in which pre-natal axon miswiring can be corrected and appropriate definition of cortical areas rescued: this period was disrupted by pre-term birth and dysregulation of serotonin levels. This work may have profound implications for our understanding of human neurodevelopmental disorders that occur in extremely pre-term infants.

You can find out everything you need to know by downloading the full text here: Plasticity of thalamocortical axons is regulated by serotonin levels modulated by preterm birth | PNAS

Well done to everyone involved in this groundbreaking study – it was a pleasure working with you and we look forward to learning how this work progresses in the future!

In Client successes

Researchers land Horizon Europe funding to tackle the burden of sepsis

Earlier this year, we had the great pleasure of working with Jan Frič and colleagues on their Horizon Europe proposal that aims to raise awareness and tackle the long-term consequences of sepsis.

We are delighted to share the news that this hugely exciting proposal has now been awarded a staggering 6.9 million euros! The consortium involved are already hard at work kick-starting their 5-year project titled “Biomarkers established to stratify sepsis long-term adverse effects to improve patients’ health and quality of life” – aka “BEATsep”.

We can’t wait to see how BEATsep progresses and to work with the team on their research outputs in the near future. For more information, check out their post below and their website: www.beatsepsis.eu

Huge congratulations to everyone involved!

In Blog

At the start of the year, we launched our “fresh look” grant editing service. We have already started working with many of you and look forward to learning the outcome of your proposals later in the year. Meanwhile, IEL’s Director and senior editor Dr. Neil McCarthy has put together a three-part blog on “How to write winning grant applications”.

About Neil

Before finding out what Neil has to say in part one of his blog, let’s find out why he is ideally placed to provide IEL clients with some useful hints and tips on successful grant writing!

Many of you will know Neil as a senior editor with Insight Editing London (IEL), but he is also a Lecturer in Immunology / MRC Career Development Fellow in the Faculty of Medicine at Queen Mary University of London. Neil is Research Lead in The Blizard Institute’s Centre for Immunobiology, as well as Infection and Inflammation Lead in the cross-faculty Centre for Predictive in vitro Models. He has secured more than £1M in personal research funding to date, including research council grants, via charitable sources, and through various commercial projects. Let’s hear what Neil has to say, in part two of his blog, “Time – Team – Tools“.

Time – Team – Tools

“A key component of biomedical grant writing is clearly outlining the important scientific or clinical problem that you are ultimately trying to ‘fix’. In your proposal, you will need to convince a reviewer that this is the best possible time, team, and tools you could need to tackle this issue. For conventional project grants, this involves identifying a major current challenge in biomedicine, breaking this down into competent parts, and then securing the best possible collaborative partners and research tools to address each separate element.

If your own research team lacks a key skill, it is important to forge links with other labs that have the required track record to cover that need. In an ideal situation, each project aim will also be linked but not dependent on the others, so that if any one aspect of the study fails there will still be useful outputs from other areas. At the same time, a compelling grant proposal will also have a clear ‘narrative arc’ that ties the individual pieces together, thereby appearing to build towards your ultimate goal of ‘curing disease x’ (or at least making some progress in this direction).”

Stay tuned for part two that discusses the importance of the “Person, Project, and Place”!

In News

New findings on how pulmonary metastases form in gastric cancer (GC) have been published in the Journal of Cellular Biochemistry!

Ming Wang and colleagues at Henan University, investigated how extracellular vesicles known as exosomes might help GC cells metastasize to the lungs, using mouse forestomach carcinoma cells as their model system. They found a novel mechanism by which GC-derived exosomes mediate PD-L1 expression in lung macrophages (which helps cancer cells evade immune detection), which in turn facilitates lung pre-metastatic niche formation. Wang et al. hypothesize that these findings might one day translate into a future potential therapeutic target for GC with pulmonary metastases.

Find out more, here: https://onlinelibrary.wiley.com/doi/10.1002/jcb.30390

Well done to the authors involved in this insightful study – it was a pleasure to work with you and learn more about this exciting research!