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Holobiont

Holobiont

By Ursule Demael
A podcast at the crossroads of microbiology, immunology, evolution, computational biology and more. Through informal interviews with researchers and students, I explore how biological organisms are "holobionts": super-organisms formed by a host and all of its communities of micro-organisms ( bacteria, viruses, fungi...)
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#19 Stochastic Models of Evolution (Amaury Lambert)

Holobiont

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#20 Philosophy of Immunology and the Biological Self (Thomas Pradeu)
Thomas Pradeu is a CNRS Research Director in Philosophy of Science, leading a group at the ImmunoConcept called Conceptual Biology and Medicine. His group explores conceptual aspects spanning immunology, evolutionary biology, ageing and the microbiome.  We discuss: What Philosophy of Immunology is  How to assess the influence of an idea Misconceptions about the immune system The usefulness of the self/non-self framework Definitions of cancer in multicellular organisms How to integrate philosophy in science The ImmunoConcept lab page: https://immunoconcept.cnrs.fr
53:52
July 28, 2022
#19 Stochastic Models of Evolution (Amaury Lambert)
Prof Amaury Lambert is a mathematician, leading a research group called SMILE (Stochastic Models for Inference of Life Evolution) at the Collège de France in Paris. He is also a Professor at the Ecole Normale Superieure in Paris.  In this conversation, we discuss Mathematical definition of species Modelling the birth and death of species Using DNA sequences to infer common ancestors and species history Contingency in evolution Beauty in mathematics vs biology SMILE webpage: https://smile.cnrs.fr SMILE webpage at the Collège de France : https://www.college-de-france.fr/site/en-cirb/lambert.htm
50:11
June 09, 2022
#18 Tracking Emerging Viruses (Miles Carroll)
Miles Carroll is leading a research group on High Consequence Emerging Viruses at the University of Oxford, and has previously worked at Oxford Biomedica and as head of research at Public Health England (PHE). This episode focuses on emerging viruses, which are viruses like coronaviruses and Ebola virus that have rising incidence or are increasing in distribution. We discuss: What makes an emerging virus successful Fieldwork during the West African Ebola outbreak (2013-2016) Using Nanopore sequencing and molecular epidemiology to track emerging viruses How to deal with the threat of future spillover events Miles Carroll Lab Page : https://www.well.ox.ac.uk/research/research-groups/carroll-group
53:09
May 09, 2022
#17 Bacteriophage Therapy against Cholera (Minmin Yen)
Dr Minmin Yen (PhD) is the co-founder and CEO of PhagePro, an early stage bio-tech company spun out of the Camilli lab at Tufts University developing bacteriophage prophylactics against cholera, a diarrhoeal disease caused by Vibrio cholerae. Minimin Yen has been recognised by the MIT's Tech Review as 35 innovators under 35 for her work bridging biological engineering and public health.  In this conversation we discuss: The evidence that bacteriophages play a role in cholera epidemics The strategy of delivering lytic bacteriophages to prevent person-person transmission How we can compound the emergence of resistance in cholera bacteria Building trust in communities for adoption of experimental therapies The challenges of developing a biotech and manufacturing bacteriophage prophylactics Link to the PhagePro website: https://www.phageproinc.com Minmin Yen's MIT Tech Review article : https://www.innovatorsunder35.com/the-list/minmin-yen/
43:27
March 03, 2022
#16 Trained Immunity (Mihai Netea)
Prof. Mihai Netea is Head of the Division of Experimental Medicine at Radboud University (Netherlands) and group leader associated with the LIMES Institute in Bonn (Germany). He was the first to describe trained immunity, the ability of the innate immune system to display enhanced responsiveness to secondary stimuli. His group has studied the epigenetic modifications and metabolic reprogramming in trained immunity, especially in the context of BCG vaccination.  We discuss: Challenging dogma in immunology The epigenetic signatures and metabolic reprogramming occurring in trained immunity The evolutionary importance of trained immunity  Drug repurposing and nano-biologics to therapeutically target trained immunity  Rational use of trained immunity in vaccination strategies 
38:19
December 08, 2021
#15 Atypical T cell responses: HLA-E Immunology (Sir Andrew McMichael)
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: Prof McMichael's career in immunology spanning from his work in the 1980s on HLA restriction and recognition of viral peptides to the study of a HLA-E, an atypical MHC-Ib molecule that is involved in immunosurveillance  How HLA-E is involved in detection of the "missing self" by Natural Killer (NK) cells  The discovery of a class of CD8+ T cells recognising HLA-E complexes and their role in protection against SIV infection  The opportunities and unanswered questions in  HLA-E immunobiology Advice to scientists 
50:36
November 25, 2021
#14 Host-Mycobacterium tuberculosis interactions ( Sarah M. Fortune)
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 How bacterial and hosts determinants contribute to variability of outcomes A genome-wide strategy using CRISPR to identify target genes influencing the response to mycobacterial infection in macrophages The emerging roles of antibodies in the protection against TB disease The potential of technology-driven science in pushing the TB field forward 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
38:28
October 27, 2021
#13 Physics of Biological Evolution and Simplicity Bias ( Ard Louis)
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 The historical role of theoretical physics in the life sciences The bias towards biological structures with low descriptional complexity  The concept of "Arrival of the Frequent" in evolution The usefulness of mathematics in describing biology 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
01:01:00
October 04, 2021
#12 Medieval Parasites: Bio-Archaeology ( Patrik Flammer)
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
41:43
September 27, 2021
#11 CRISPR AntiMicrobials ( David Bikard)
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/
51:18
September 13, 2021
#10 Cancer et al : Tumour microbiome and immune micro-environment (Matteo Massara)
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:  how tumour inflammation can be targeted for treatment  how bacteria in our microbiota can drive cancer progression even at distant sites via gut-brain communication   the challenges of  studying tumour environments when so many factors and variables are involved 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!
35:01
August 06, 2021
#9 Polio Eradication (Ellyn Ogden)
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
49:38
July 25, 2021
#8 BioArt, Beauty and The Bacterial Sublime (Anna Dumitriu)
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
59:06
July 09, 2021
#7 The Multiple Lives of Toxoplasma gondii (Pascale Guiton)
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: Neuroinflammation- associated alteration of fear in mice: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963786/ Enzymes determining host range for sexual reproduction:   https://pubmed.ncbi.nlm.nih.gov/31430281/ The MORC protein in sexual commitment: https://www.nature.com/articles/s41564-020-0674-4 To follow up on Pascale Guiton's research: https://guitonlab.com
38:46
July 02, 2021
#6 Back to the Structure: RNA Secondary Structure in Viral Infections (Louisa Iselin)
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. 
37:30
June 22, 2021
#5 Co-infections: Cytomegalovirus and M. tuberculosis (Shuailin Li)
Shuailin Li, a PhD Student at the Jenner Institute in the group of Prof Helen McShane, studies the link between cytomegalovirus (CMV) infection and M.tuberculosis infection or tuberculosis(TB) disease. Infections rarely, if ever, happen in isolation: humans are infected with 10 chronic viruses on average and this imprint shapes our response to other pathogens.   On this episode, find out how data from a vaccine study cohort uncovered a detrimental association between CMV infection and TB, the likely immunological mechanisms for this effect and the possible implications of these findings in endemic regions. 
19:36
June 10, 2021
#4 Of Birds and Viruses: Avian Influenza ( Holly Everest)
Holly Everest, a DPhil Student working at the Pirbright Institute and previously a researcher at the Animal&Plant Health Agency, speaks about her research on avian influenza viruses. This episode explores the limitations of vaccines and antivirals to treat avian influenza, how epidemiological surveillance is conducted, how to predict whether avian influenza viruses are of pandemic concern and generally how influenza viruses are good at what they do....
37:36
June 02, 2021
#3 Applying bio-organic chemistry to overcome antibiotic resistance ( Nicola Wade)
Nicola Wade, a 3rd year PhD student at Leiden University, shares her research on using the tools of chemistry to optimise antibiotic compounds and combat antibiotic resistance. This episode includes discussion on developing novel beta-lactamase inhibitors, challenges of developing narrow-spectrum antibiotics and the importance of science communication around antibiotic resistance.  *** Music: "Fossiles" from the Carnival of the Animals (Saint Saëns). Recording by Seattle Youth Symphony, used under a Creative Commons Attribution-Share Alike 2.0 Generic license.
30:37
May 15, 2021
#2 Host directed therapies against HIV (Kate Dicker)
This episode covers how RNA binding proteins can be targeted to antagonise viral infection, the challenges of host-directed therapies against HIV and promising future directions in the field of HIV/AIDS. Kate Dicker, a PhD student in Infection, Immunology and Translational Medicine at the University of Oxford, shares her research. *** Music: "Fossiles" from the Carnival of the Animals (Saint Saëns). Recording by Seattle Youth Symphony, used under a Creative Commons Attribution-Share Alike 2.0 Generic license
21:27
May 09, 2021
#1 Paleovirology: The Evolutionary History of Viruses (José G. Nino Barreat)
This episode explores how genomics can be used to study ancient viruses, how viruses have provided benefits to their hosts over the course of evolution and how knowledge of virus evolution could have applications in genetic engineering and pandemic preparedness. I interview José Gabriel Niño Barreat, a DPhil candidate in Zoology at the University of Oxford.  *** Music: "Fossiles" from the Carnival of the Animals (Saint Saëns). Recording by Seattle Youth Symphony, used under a Creative Commons Attribution-Share Alike 2.0 Generic license.
36:47
May 02, 2021