Blog posts

Revolution rather than evolution? A journal club discussion on the use of gene editing based on the Netflix documentary series “Un-natural selection”

Written by Patricia Ogger

Edited by Max Kirtland

For millennia, humans have attempted to control nature to select traits in animals, change the environment, and eliminate infections and disease. In the last decade, the discovery and utilisation of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system has provided us with a specific, efficient and cheap method to change nature instantly at the genetic level (see schematic for details – Doudna & Charpentier, 2014, Science).

The explosion in the use of CRISPR, and the societal and environmental implications of this and other gene editing techniques were recently covered in the Netflix documentary “Un-natural selection”, by filmmakers Joe Egender and Leeor Kaufman.

Modulation of the gut microbiota in infants at high risk for asthma by Lactobacillus supplementation

By Rachele Invernizzi

The human gut is home to trillions of microorganisms that exert a marked influence on the host in homeostasis and disease. Research within the microbiome field is advancing at a rapid pace; recent work has shown that the composition and function of the gut microbiota are symbiotically linked with host health, and altered in several immune-mediated disorders, including asthma. With the intention of modulating the intestinal microbiota, early probiotic administration has been used for the prevention of allergic diseases in infants, with variable success.

Durack and colleagues (1) wanted to explore the maturation of gut microbiota over the first year of life in infants at high risk for asthma, and whether it was modifiable by early-life Lactobacillus rhamnosus GG (LGG) supplementation.

The gut microbiome: a trigger for asthma in childhood?

By Rachele Invernizzi

The human microbiome is composed of approximately 100 trillion bacteria and our intestinal tract is where the majority of these bacteria reside. The gut microbiota and their metabolic products exist in a dynamic state, which varies throughout the lifetime of the individual. This is particularly true during the first 18 months of life as the gastrointestinal tract becomes colonised and communities of bacteria form in various niches throughout the gut. There is a growing appreciation that the gut microbiota plays a vital role in host physiology as well as in the pathophysiology of several disorders, including asthma.

The primary objective of this study (1) was to phenotype the gut colonisation patterns during the first year of life and the associations of these patterns with the later risk of asthma in a prospective cohort of 700 children.

Type 2 innate lymphocytes guard against acute lung injury

Written by Chloe Pyle

Edited by Lauren Headley

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause, which results in hardening of the lung parenchyma due to collagen deposition and loss of pulmonary function. The role of the immune system in lung fibrosis is not well defined, although previous studies have shown that immune suppression is associated with decreased survival in acute exacerbations of IPF. The new study we discussed (1) addresses the contribution of population of immune cells, those that express the molecule ICOS, on the outcome of acute lung injury in a mouse model of lung injury and fibrosis.

TLR4 localization: Shaping inflammation is a battle of the lineages

By Dhiren Patel

Edited by Chloe Pyle and Faith Uwadiae

In the recent ‘Compare & Contrast’ journal club, we had the pleasure of discussing two excellent papers based on the immunopathological roles of Toll-like Receptor 4 (TLR4). The two papers presented the importance of the localisation of TLR4 on stromal or haematopoietic cell types and their contribution in inducing pathology in different airway disease models.

Toll-like receptor 4, is a pattern-recognition receptor that is expressed on array of cells and a common agonist for this receptor is Lipopolysaccharide (LPS), a sugar molecule highly expressed on gram negative bacterial cells1. The importance of TLR4 expression on immune cells such as granulocytes, neutrophils and eosinophils in driving an immune response against various pathogens has been published on extensively.

Chemokine cascades drive the education of metastasis-promoting macrophages

Written by Caroline Anderson

Edited by William Foster and Arunon Sivananthan

This week we were fortunate enough to welcome a world-renowned biomedical scientist to the IRD journal club. Professor Jeffrey Pollard is currently the Director of the Medical Research Council Centre for Reproductive Health at the University of Edinburgh. His seminar earlier in the day had focussed on the role of the tumour microenvironment, and metastasis-associated macrophages (MAMs) in particular, in breast cancer metastasis. Much of the work he discussed can be found here: Kitamura et al, JEM, 2015 (PMID: 26056232).

Both pro- and anti-tumorigenic immune cells are found in association with tumours.

Hold your nerve; a new way to halt MPN progression

Written by William Foster

Edited by Judith Secklehner

On Monday the 15th of February the NHLI welcomed Dr Simón Méndez-Ferrer for a lunchtime seminar. Dr Méndez-Ferrer has recently moved from Madrid to Cambridge, where he has established a group in the Haematology department. Dr Méndez-Ferrer studies the multisystem regulation of the haematopoietic stem cell niche and his work has clinical implications for bone marrow transplantation procedures, as well as insight into specific forms of leukaemia. In Simón’s talk he discussed haematopoietic stem cell trafficking; paying attention to the importance of microenvironments; with focus on the importance of neural signal modulation within the bone marrow and how Mesenchymal Stem cells(MSCs) regulate inflammatory cell trafficking.

Insights into the life cycle of filarial parasites

Written by William Branchett

Edited by John Mackey

IRD recently hosted Dr Coralie Martin from the Muséum National d’Histoire Naturelle in Paris, who led a seminar and Journal Club on her research of the dynamics of filarial parasite infection. Filariae are nematodes that can cause debilitating and disfiguring diseases such as river blindness, which affects around 37 million people in Africa. Dr Martin utilises the rodent filarial parasite Litomosoides (L.) sigmodontis in mouse models to identify novel strategies for intervention in filarial infection.

In her seminar, Dr Martin focused on the life cycle of L. sigmodontis, which begins by intradermal delivery of larvae via an insect bite.

Getting enough iron in their diet: macrophages develop specialized protective functions within atherosclerotic plaques

Written by Khansa Hussain

Edited by Caroline Anderson

Last November we had the pleasure to welcome Dr Joseph Boyle from Imperial College London to our IRD Journal Club. He nominated his publication “Activating Transcription Factor 1 Directs Mhem Atheroprotective Macrophages Through Coordinated Iron Handling and Foam Cell Protection” to introduce and discuss with us his interesting finding of identifying a unique state of macrophages (Mhem) within intraplaque hemorrhage (IPH). IPH is a common feature of atherosclerotic plaque damage which involves the rupture of neovessels causing blood to escape into the surrounding tissues. This leads to cholesterol and heme/iron loading. The monocytes that enter the plaques and differentiate to macrophages to clear hemorrhage-related iron or lipid are known as Mhem macrophages to discriminate them from the classic lipid-laden macrophages (foam cells).

Neutrophils know when to cast a wide NET

Written by Dhiren Patel

Edited by Judith Secklehner and John Mackey

We recently had the pleasure of attending a great seminar by Dr. Venizelos Papayannopoulos of the Francis Crick Institute titled “Decision making neutrophils in antimicrobial responses”.

He introduced the audience to Neutrophil Extracellular Traps (NETs) which are large web-like structures consisting of neutrophil cellular components post necrosis. NETs consist primarily of histones but also contain a large proportion of the potent arsenal of granular components that neutrophils commonly utilise to kill and digest pathogens.

Dr. Papatannopolous then introduced us to the first of 2 papers he discusses in the seminar titled “Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens1”.