Revolutionizing Neural Circuit Analysis with Optogenetics

We were delighted to see that the latest findings from Adam Claridge Chang’s lab published in Nature Communications in April, were covered in The Straits Times just last week!

In case you missed it in April and would like to add this paper to your summer reading list, you can find the article here: https://www.nature.com/articles/s41467-024-47203-w#Sec17

So, what’s it all about?

Light-gated, chloride-conducting anion channelrhodopsins (ACRs) are powerful neuron inhibitors. The problem is that for cells with high intracellular chloride concentrations, ACRs may have an activating rather than inhibitory effect. So, Adam Claridge-Chang and colleagues aimed to find an alternative optogeneic approach to using ACRs. Enter, potassium-conducting kalium channelrhodopsins (KCRs)!

What did they find?

The research team evaluated the ability of KCRs to inhibit neural activity and suppress behavior in three model organisms: Drosophila, Caenorhabditis elegans, and zebrafish. They found that a variant of KCR1, with improved plasma-membrane trafficking, showed comparable potency to ACR1 but with enhanced properties, including reduced toxicity and better efficacy in high-chloride cells.

What does this mean?

KCRs could be considered next-generation optogenetic inhibitors, opening new avenues for in vivo circuit analysis in small, genetically tractable animals.

Congratulations to the whole team who worked on this exciting project – and for the exciting coverage in The Straits Times: https://www.straitstimes.com/singapore/duke-nus-researchers-develop-light-controlled-switch-for-brain-cells-to-better-study-the-brain

#Neuroscience #Optogenetics #ResearchInnovation #NeuralCircuits #KCRs #ACRs #InVivoAnalysis #Biotechnology

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

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:
https://lnkd.in/eJzsu4gC

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!

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!