Holobiont

Sir Andrew McMichael is a Professor of Immunology at the University of Oxford and previously Director of the Weatherall Institute of Molecular Medicine. He is a fellow of the Royal Society and Academy of Medical Sciences and has been a leader in human immunology for decades, notably  focusing on responses to viral infections including influenza and HIV.

We discuss:

Sarah Fortune is a Professor of Immunology and Infectious Diseases at the Harvard T.H Chan School of Public Health and Director of the TB Research Program at the Ragon Institute of MGH, Harvard and MIT.

We discuss her research into the interactions between Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) and its human hosts. Specifically, we explore some approaches to explain the variability in infection and treatment outcomes, as Mtb infection remains asymptomatic in 90-95% of individuals but causes severe disease in others. 

We discuss

Prof Sarah Fortune's lab page: https://sites.sph.harvard.edu/fortune-lab/

Link to the genome-wide screening of host:mycobacterial interactions discussed ( Open Access): https://pubmed.ncbi.nlm.nih.gov/32970993/

STOP TB Partnership : http://www.stoptb.org

This episode explores the contributions of theoretical physics to understanding biological evolution and self-assembly.

Ard Louis is a Professor of Theoretical Physics at the University of Oxford and leads a group that uses computational tools to answer fundamental questions about the emergence and evolution of protein and RNA structures and gene regulatory networks. An attractive proposal developed in his recent work is that there is a bias towards simplicity in biological outputs, using the formalisation of complexity from Algorithmic Information Theory (AIT). 

We discuss

Prof Ard Louis: https://www.physics.ox.ac.uk/our-people/louis

Pre-print on the algorithmic nature of evolution :https://www.biorxiv.org/content/10.1101/2021.07.28.454038v2

Wigner's paper on mathematics in the natural sciences: https://www.maths.ed.ac.uk/~v1ranick/papers/wigner.pdf

This episode focuses on ancient parasites as a glimpse into the life of past populations. With the help of modern genomics and bio-informatics, the study of parasite samples from archaeological sites can reveal patterns about sanitation, mobility, diet and other cultural aspects of past societies. 

Dr. Patrik Flammer, a postdoctoral researcher at the University of Oxford, speaks about a collaborative project sampling intestinal helminths ( a type of parasitic worm), from medieval graveyard sites across the UK, Germany and the Czech Republic. 

We discuss the challenges of studying ancient DNA (aDNA), the information that parasite identity and diversity can provide and the "hygiene hypothesis",  briefly exploring how decreased prevalence of parasites has been linked to a rise in allergies and auto-immune diseases.

The study about the Epidemiology of Intestinal Helminths in Medieval Europe (Open Access) https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008600

Another study using archaeoparasitology to illuminate trading patterns in Medieval Lübeck ( Open Access) https://royalsocietypublishing.org/doi/10.1098/rspb.2018.0991

Link to Dr Patrik Flammer and Dr Adrian Smith's profiles to get into contact

https://www.zoo.ox.ac.uk/people/dr-patrik-flammer#/

https://www.zoo.ox.ac.uk/people/dr-adrian-smith#/

An article about Composting Human Remains : https://www.newyorker.com/magazine/2019/09/02/everything-youre-afraid-to-ask-about-human-composting

Dr. David Bikard is pioneering the use of CRISPR-Cas genetic systems re-programmed to target specific pathogenic or antibiotic resistant bacteria. This feat of ultra-precise genetic engineering represents a big shift from current approaches using broadly acting antibiotics that favour the spread of resistance and disturb the microbiome. 

David Bikard is the head of the Synthetic Biology Lab at the Institut Pasteur and also founded Eligo Biosciences, a biotech that is pushing for the translation of CRISPR based therapeutics to modify the microbiome. 

In this conversation, we discuss the phagemid technology using bacteriophage components to deliver CRISPR-Cas systems in bacteria, the hurdles to translate findings in vivo as well as the power of technology-driven science. 

"Progress in science depends on new techniques, new discoveries and new ideas, probably in that order"  Sydney Brenner

Links to David Bikard's lab:  https://research.pasteur.fr/en/team/synthetic-biology/

Eligo Biosciences: https://eligo.bio

And to the paper on sequence specific killing of Staphylococcus aureus : https://pubmed.ncbi.nlm.nih.gov/25282355/

Tumours are not just self sustained masses of proliferating cancer cells! Tumours are cloaked in a "micro-environment" of immune cells like macrophages and neutrophils and even bacteria, as tumours also have their distinct microbiome, which plays a key role in shaping the outcomes of cancer.

Matteo Massara, a post-doctoral research at the University of Lausanne (UNIL, Switzerland) studies the complexity of the immune micro-environment of tumours. In this episode, we discuss:

This episode is by no means exhaustive as the field of inflammation and microbiome in cancer is exploding but will hopefully give you a flavour of what lies at the intersections of microbiology and cancer immunology. It also reminds us that we should never forget to consider the micro-organisms within us as a key players in all aspects of our physiology, normal or abnormal, including cancer!

Ellyn Ogden has been leading the polio eradication campaign for USAID for over 20 years and shares some powerful stories that shed light on the challenges that have surfaced along the way. 

From addressing vaccine hesitancy in different cultural settings, to negotiating cease fires with rebel groups in the Democratic Republic of Congo and responding to the issue of OPV vaccines reverting back to virulence, the road to polio eradication has not been smooth.

In 1998, polio was actively circulating in 125 countries and in 2021, it is endemic in just two countries. This is a tribute to the achievements that can stem from effective worldwide collaboration, attentive public healthy policy and the motivation of key individuals eager to implement positive change. 

If you wish to donate and support the polio eradication efforts:

https://www.rotary.org/en/donate

https://www.unicef.org/immunization/polio

Anna Dumitriu is an internationally renowned Bio-Artist who has pioneered artistic creations threading the fields of microbiology and infectious diseases, synthetic biology as well as artificial life and intelligence.

On this special episode, we explore her conception of the "sublime" in the bacterial world, bacteria as vessels of poetry and beauty, symbiosis in the living world and whether we should anthropomorphise biology ( with detours via the history of antibiotics, neural networks and what it means to be living)

Some of her projects that we discuss include "Make Do and Mend", "Archaeabot", "HyperSymbiotics" and "Fermenting Futures", links to which can be found on her main website https://annadumitriu.co.uk

Dr Pascale Guiton, an Assistant Professor at California State University, tells us about the fascinating biology of Toxoplasma gondii, a widely spread protozoan parasite that infects most warm blooded mammals and can cause severe disease in foetuses and immunocompromised hosts. 

We discuss how Toxoplasma gondii can modulate the behaviour of its hosts, why its sexual reproduction cycle only occurs in felines, the inflammatory response it elicits and its complex mechanisms of genome regulation.

A diagram of the complex life-cycle of the parasite will be helpful to follow this discussion (https://www.researchgate.net/figure/Life-cycle-of-T-gondii-Sexual-and-asexual-reproduction-of-Toxoplasma-take-place-in_fig1_337784380) 

Links to the articles discussed:

To follow up on Pascale Guiton's research: https://guitonlab.com

Louisa Iselin, a PhD Student at the University of Oxford, speaks about her fundamental research on viral RNA structures and how they interact with host RNA binding proteins.

RNA is not just a "squiggly line", like textbook diagrams could lead us to believe, but adopts higher order secondary structures that influence key steps in viral pathogenesis, including sensing by the innate immune system. 

This episode explores the association of distinctive RNA structures with persistence of viruses in their hosts, what CpG dinucleotide patterns are and how they could affect viral fitness, and how proteomics and computational approaches are used to make sense of protein-RNA interactions.