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
How to write winning grant applications: Part 3
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”.
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!): firstname.lastname@example.org
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!
Veterinary mycoplasmas: updates and knowledge gaps
We are so excited to present this latest research report, commissioned by the US Department of Agriculture (USDA) Agricultural Research Service (ARS) and STAR-IDAZ International Research Consortium on Animal Health and authored by our own Daniel Ackerman, Laura Roden and Lucy Robinson.
Our team was given the challenge of reviewing all the literature on veterinary mycoplasmas of interest (3500 papers!), selecting those studies that presented important findings, and collating the data from the field into a coherent and engaging summary document that can be used by researchers and policy-makers to help identify important knowledge gaps.
We are super-proud of this work, and have high hopes that it will be a significant help in guiding resources to those areas most in need of further research.
Thanks again to the commissioning team at STAR-IDAZ International Research Consortium on Animal Health for your support during the writing, and to all the researchers who reviewed and made suggestions to improve the report along the way: Georgina Grell, Madeline Newman, Alex Morrow, Nicholas Juleff, Roxann Brooks Motroni DVM, PhD, Rachel Wood, Mark Ackerman, Jeff Caswell, Rohana Dassanayake, Jeff Evans, Patrice Gaurivaud, Bryan Kaplan, Dominiek Maes, Musa Mulongo, Robin Nicholas, Jose Perez-Casal, Sacchini Flavio, Massimo Scacchia and Dan Tucker.
You can read the full report here:
This is not the first time the IEL team have been involved in compiling literature reviews – in fact, it is becoming quite a specialty! We really enjoy digging deep into a subject area and teasing out the ongoing issues and areas for future research. Get in touch if you would like support on a literature review for your topic of interest!
Findings published in Frontiers in Immunology earlier this year show that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies!
Marcela Hortova-Kohoutkova and colleagues aimed to understand whether the dynamics of iron regulation could be used as a biomarker for inflammatory disease severity. In their cohort, comprising patients with #septicshock and #covid19, they saw that elevated hepcidin levels reflect overall immune-cell activation driven by intrinsic stimuli, while ferritin levels were boosted by pathogen-induced inflammation.
Hortová-Kohoutková et al. ultimately propose that the hepcidin-to-ferritin ratio could identify those at risk of mortality in septic shock. These findings have amazing clinical potential and we are really excited to see how they translate going forward!
Check out the full, open-access article here: https://lnkd.in/e8XYBsg9
Congratulations to the whole team involved in this work – Insight Editing London’s Daniel Ackerman enjoyed working with you all on this paper!
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!