In Client successes

New publication success!

A collaborative team of researchers based at the Shanghai Institute of Immunology, the First affiliated hospital of Zhejiang University, the Singapore Immunology Network, the National University of Singapore (NUS), and the SingHealth Duke-NUS Academic Medical Center, have published the results of a superb study into how mutations in CSF-1R affect microglia to promote neurodegenerative disease.

The focus of this study was hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) – a rare yet fatal neurodegenerative disease underpinned by mutations in CSF-IR. Wei Jie Wong and colleagues developed a state-of-the-art macrophage and forebrain organoid co-culture derived from induced pluripotent stem cells isolated from two patients with HDLS.

Compared to control organoids (in which CSF-1R gene mutations were corrected), they found that the patient-derived macrophages exhibited a metabolic shift towards the glycolytic pathway and reduced CSF-1 sensitivity. The result of this shift was an increase in IL-1β production and an activated inflammatory phenotype. RNA sequencing revealed that these macrophages existed in a reactive state, which led to impaired neuronal cell regulation.

This ground breaking study has provided yet more evidence of the diverse roles of microglia, as well as great insight into the pathological mechanisms of HDLS. We have no doubt that immunologists, neuroscientists, and clinicians will all be thrilled to read this exciting study and learn how Wei Jie Wong et al. tackled this complex question.

If you are interested to learn more, the paper is now available to download here, complete with referee reports:

Many congratulations to the whole team: Wei Jie Wong, Yi Wen Zhu, Hai Ting Wang, Jia Wen Qian, Ziyi Li, Li Song, Zhao Yuan Liu, Wei Guo, Shuang Yan Zhang, Bing Su, Fang Ping He, Kang Wang and Florent Ginhoux!

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:

Huge congratulations to everyone involved!

In Client successes

Publication Success!

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:

Congratulations to the whole team involved in this work – Insight Editing London’s Daniel Ackerman enjoyed working with you all on this paper!

In Client successes

Publication success!

Congratulations to Deola Sara and colleagues at Sidra Medicine (Qatar) and the Università degli Studi del Piemonte Orientale (Italy) on their recent publication in Blood Advances just last month!

Deola and colleagues conducted an impactful study to improve #genetherapy approaches for #hemophilia. For those of you unsure, hemophilia is a bleeding disorder that occurs as a result of a blood-clotting protein deficiency or dysfunction. Treatment options are currently limited, but progress has been made in recent #clinicaltrials that have looked at replacing the blood clotting protein factor VIII in autologous hematopoietic stem cells (HSCs) using viral delivery systems.

Here,  Deola et al. identified exactly which cell types should be targeted for such gene therapy, by looking at which HSCs and their progeny produce factor VIII. They achieved this by leveraging a flow cytometry method to generate a comprehensive map of native and lentivirus-based transgenic factor VIII production right from the HSC stage to the mature blood cell stage. Their map showed that factor VIII is produced during the progenitor-cell stages after cytokine stimulation. In the mature blood-cell stages, monocytes are responsible for most factor VIII production.

Moving to a zebrafish model of transient HA to validate their findings, Deola et al. found that promoting HSC self-renewal by treating these cells with the agonist UM171 resulted in the specific expansion of CD14+/CD31+ monocytes. These monocytes could carry the factor VIII transgene, thus correcting HA in zebrafish!

These findings might signal an advance towards a permanent treatment for patients with HA! Check out the details here:

Well done to everyone involved in this really exciting project: Insight Editing London’s Ilya Demchenko really enjoyed getting a sneak peek of these results before submission and assisting with the editing.

In Client successes

Publication success!

Hot off the press: a new review article has been published in Trends in Paristology on helminth infections in cattle.

Here, Johannes CharlierDiana WilliamsNadine Ravinet and Edwin Claerebout discuss how by combining refined diagnostic thresholds with farm-specific information on grazing systems and animal history, farmers can tailor helminth treatments to ultimately limit anthelmintic resistance and boost agricultural efficiency and food security.

You can access the paper here if you would like to find out more:

Congratulations to all those involved in this interesting article – it was a pleasure working with you!

In Client successes

Publication success!

Chao Liu and colleagues have yet another reason to celebrate! Earlier this year, Liu et al. published the results of their single-cell RNA sequencing analysis of paired pre- and post- radiochemotherapy (RCT) tumor biopsies from patients with cervical cancer.

Their findings, published in the journal Signal Transduction and Targeted Therapy, showed that compared to pre-RCT, post-RCT samples exhibited residual epithelial cells expressing MHC class II genes. Here, they also saw accumulated monocytic myeloid-derived suppressor cells with pro-inflammatory features, and cytotoxic CD16+ natural killer cells. These findings implicate innate immune system activation in cervical cancer after RCT.

This paper serves as an excellent resource, detailing the complexity of the tumor ecosystem and its response to RCT. We are sure that numerous lines of research into new and improved treatments for affected patients will stem from the important findings detailed in this study.

Take a deeper look:

Well done to everyone involved in this excellent work!