Zika: Cellular mechanisms of microcephaly due to Zika virus infection in mice
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Since October 2015, the occurrence microcephaly has dramatically increased in South
America, a phenomenon that has been tied to the widespread epidemic of the Zika virus
(ZIKV). However, as correlations does not imply causation, we aim to investigate this
relationship by studying the anatomical and cellular brain alterations caused by the ZIKV at
different gestational stages.
Microcephaly is a severe brain malformation defined as a head circumference more than two
standard deviations below the mean that can be associated with decreased neuronal
production due to proliferation defects and death of cortical progenitors. It is called primary
microcephaly when diagnosed before the 36th gestation week. The known causes vary from
genetic mutations, such as MCPH1-MCPH11, to extrinsic insults such as the so-called TORCH
factors: Toxoplasmosis, Rubella, Cytomegalovirus (CMV) and Herpes.
We aim to model microcephaly using in utero injection of ZIKV in pregnant mice during the
peak of foetal neurogenesis. We will be able to determine the capacity for ZIKV infection to
produce microcephaly and compare the cellular mechanism of injury with other well-known
causes such as CMV and downregulation of MCPH6.
This project will shed light on the etiological nature of ZIKV infection for microcephaly, using
an animal model simulating the human condition. In addition, it will define the critical
developmental period for ZIKV infection, characterize the morphological abnormalities in
brain anatomy with high-resolution magnetic resonance, and unfold the developmental
processes impaired by ZIKV infection.
America, a phenomenon that has been tied to the widespread epidemic of the Zika virus
(ZIKV). However, as correlations does not imply causation, we aim to investigate this
relationship by studying the anatomical and cellular brain alterations caused by the ZIKV at
different gestational stages.
Microcephaly is a severe brain malformation defined as a head circumference more than two
standard deviations below the mean that can be associated with decreased neuronal
production due to proliferation defects and death of cortical progenitors. It is called primary
microcephaly when diagnosed before the 36th gestation week. The known causes vary from
genetic mutations, such as MCPH1-MCPH11, to extrinsic insults such as the so-called TORCH
factors: Toxoplasmosis, Rubella, Cytomegalovirus (CMV) and Herpes.
We aim to model microcephaly using in utero injection of ZIKV in pregnant mice during the
peak of foetal neurogenesis. We will be able to determine the capacity for ZIKV infection to
produce microcephaly and compare the cellular mechanism of injury with other well-known
causes such as CMV and downregulation of MCPH6.
This project will shed light on the etiological nature of ZIKV infection for microcephaly, using
an animal model simulating the human condition. In addition, it will define the critical
developmental period for ZIKV infection, characterize the morphological abnormalities in
brain anatomy with high-resolution magnetic resonance, and unfold the developmental
processes impaired by ZIKV infection.
People |
ORCID iD |
Publications
Barbeito-Andrés J
(2020)
Congenital Zika syndrome is associated with maternal protein malnutrition.
in Science advances
Chimelli L
(2017)
The spectrum of neuropathological changes associated with congenital Zika virus infection.
in Acta neuropathologica
De Souza AS
(2018)
Imaging findings in congenital Zika virus infection syndrome: an update.
in Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
Delvecchio R
(2016)
Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models.
in Viruses
Garcez P
(2017)
Zika virus disrupts molecular fingerprinting of human neurospheres
in Scientific Reports
Garcez PP
(2018)
Zika virus impairs the development of blood vessels in a mouse model of congenital infection.
in Scientific reports
Garcez PP
(2016)
Zika virus impairs growth in human neurospheres and brain organoids.
in Science (New York, N.Y.)
García-Moreno F
(2020)
Variations of telencephalic development that paved the way for neocortical evolution.
in Progress in neurobiology
Gilbert-Jaramillo J
(2019)
The potential contribution of impaired brain glucose metabolism to congenital Zika syndrome.
in Journal of anatomy
| Title | Art of Anatomy |
| Description | This is a paper on the link between anatomy and art: This paper arose from exhibitions in Oxford and Dublin and comprises three experiments which look at the relationship between anatomy and art. In the first experiment, a passport photograph, photographic portrait and portrait in oils, all of the same sitter, show how artistic input transforms anatomy from a mere likeness into works of art. In the second, the reverse is true, as computer techniques render idealized old master images anatomically accurate. The third experiment addresses the biomechanical consequences of anatomical variation and shows that vehicular design is based on mean body shapes, and so it is the average, rather than the idealized, form that is safer in a collision. |
| Type Of Art | Creative Writing |
| Year Produced | 2019 |
| Impact | This paper arose from part of The Art of Anatomy exhibition in the Kendrew Barn, St John's College Oxford which was part of the Anatomical Society Summer Meeting, 23-25 July 2018 (https://www.youtube.com/watch?v=GY1YHiYwomw). The use of anatomical distortion can aid in creating a work of art. Swan-like necks add grace to paintings, and may go undetected by the casual viewer. Marked distortions can add to the fantasy element, or idealisation, in a painting. When normal anatomy is applied, this is lost, and what remains is a mediocre academy nude, rather than great art. Car safety has radically improved in recent years by the inclusion of features based on 'average' body shapes. However, this is a one-size-fits-all approach. For those of us who are outliers, a bespoke approach is required to improve car safety. In art, anatomy may be transformed in the creation of a great work of art, and its accurate restoration can reverse the process. However, where safety is paramount, such accuracy is essential in both biomechanics and medicine. |
| URL | https://www.youtube.com/watch?v=GY1YHiYwomw |
| Title | Cajal's Interactions with Sherrington and the Croonian Lecture |
| Description | Publication on history of science in The Anatomical Record: Sherrington was a major proponent of the neuron doctrine and he was inspired by Santiago Ramón y Cajal's theory of dynamic polarization of nerve cells (Ley de la polarización dinámica de la célula nerviosa). Sherrington coined the term "synapse" to name the Cajal description of interneuronal contact and he gave the term, for functional nerve endings, as "Boutons terminaux," still used today. These two giants of neuroscience met only once, but they had a life-long friendship. It was Sherrington who wrote Cajal's Obituary for the Royal Society. We review here some of the scientific exchanges between Cajal and Sherrington, with particular attention to 1894, when the two neuroscientist met in London during Cajal's visit to deliver the Croonian Lecture to the Royal Society. We shall examine not only the scientific exchanges but also their friendship, which was immediate and strong. Anat Rec, 2019. |
| Type Of Art | Creative Writing |
| Year Produced | 2019 |
| Impact | The paper emphasises the need for European and international research collaborations: Sherrington and Cajal met only once, but they had a life-long friendship. Cajal and Sherrington shared several views on the organization of the nervous system, contiguity, importance of the synapse, and convergence and divergence of neural connections, although they devoted different importance to inhibition. The close friendship between Sherrington and Cajal lasted throughout their lives. It was Sherrington who wrote Cajal's Obituary for the Royal Society (Sherrington, 1935). |
| URL | https://anatomypubs.onlinelibrary.wiley.com/doi/full/10.1002/ar.24189 |
| Title | The Art of Anatomy Exhibition - St John's College, Oxford (July 2018) |
| Description | Art of Anatomy Exhibition, The Barn, June-July, 2018 Professor Clive Lee (Royal College of Surgeons in Ireland & Royal Hibernian Academy of Arts) Dr Sarah Simbler (Tutor of Anatomy at the Ruskin School of Art, University of Oxford) Dr Tian S. Liang (Early Career Leverhulme Fellow, St John's College) Professor Zoltán Molnár (Tutor of Human Anatomy, St John's College, Oxford) This exhibition will explore the artistic representation of anatomy during different historic periods and in different parts of the world. It will coincide with the Summer Meeting of the Anatomical Society and the Editor of Journal of Anatomy has invited papers from the anatomists and artists involved (1). Anatomy Transformed Professor Clive Lee is Professor of Anatomy at the Royal College of Surgeons in Ireland and the Royal Hibernian Academy of Arts, Visiting Professor of Biomechanics at Trinity College Dublin and has applied to be a Visiting Researcher at St John's College during Trinity Term 2018. In medicine and engineering, anatomy is applied, but in art it is transformed. Transformation by distortion is examined by comparing masterpieces, such as Ingres' La Grande Odalisque, estimated to have 3 extra lumbar vertebrae, with anatomically accurate computer images generated by Oscar winning engineer, Anil Kokaram (2,3). The balance between accuracy and artistry is explored in a triptych from passport photo to photographic portrait, by Amelia Stein RHA, to a portrait in oils by Mick O'Dea, President of the Royal Hibernian Academy of Arts www.rhagallery.ie The biomechanics of beauty will explore the practicalities of aesthetic ideals from an engineering standpoint. Finally, Anatomists, Engineers & Artists is a video installation showing the creation of an on-line 3D surface anatomy course: www.rcsi.ie/surfaceanatomy Science, History, Art Dr Sarah Simblet is a fine artist, writer, broadcaster and anatomist, Tutor in Anatomy at the Ruskin School of Art (BFA) and she teaches Short Courses in Anatomy, Botany and Drawing on the Summer School Programme (4). She is author of Anatomy for the Artist (2001), The Drawing Book (2005), Botany for the Artist (2010) and co-author of The New Sylva (2014). Sarah is dedicated to sharing and encouraging visual intelligence in others through her drawings, teaching and broadcasting worldwide. www.rsa.ox.ac.uk/people/sarah-simblet Anatomising the Body: Art, Science and the Humanities in Modern China Dr Tian S. Liang is a Leverhulme Fellow at St John's College and co-editor of Hong Ling: A Retrospective. Taipei: Soka Art (2016). She specialises in modern and contemporary East Asian art and explores understandings of human anatomy and its relations to artistic representations of the human body in China between 1851 and 1949 (5). By placing the knowledge of human anatomy at the centre of a broader nexus of artistic, medical, educational, publishing and humanitarian contexts, this project will provide the first history of the ways in which the 'body' was scientifically assessed and artistically represented across different visual media - painting, sculpture, print, woodcut and photography. https://www.leverhulme.ac.uk/awards-made/awards-focus/anatomising-body-art-science-and-humanities-modern-china-1851%E2%80%931949 Cerebral Art Professor Zoltan Molnar is Tutor of Human Anatomy at St John's College Oxford, Professor of Developmental Neuroscience at Department of Physiology, Anatomy and Genetics. His main research interest is in the development of the cerebral cortex. He has been running and organising the Neuroanatomy Practicals since 2000 at the University of Oxford. He can see art in the structure of the brain, in its histology, images. He has a huge collection of microscopic images. For some examples see (6) and for journal covers selected from Molnár Laboratories illustration see: https://www.dpag.ox.ac.uk/research/molnar-group/publications-front-covers/journal-covers |
| Type Of Art | Artistic/Creative Exhibition |
| Year Produced | 2018 |
| Impact | This exhibition will explore the artistic representation of anatomy during different historic periods and in different parts of the world. It will coincide with the Summer Meeting of the Anatomical Society and the Editor of Journal of Anatomy has invited papers from the anatomists and artists involved. |
| URL | https://www.sjc.ox.ac.uk/college-life/art/ |
| Title | The Oxford Science and Ideas Festival - The consciousness field |
| Description | https://www.dpag.ox.ac.uk/news/the-oxford-science-and-ideas-festival http://www.theconsciousnessfield.com/index.html Once again researchers from across our Oxford Neuroscience Community pulled all the stops out for the Oxford Science and Ideas Festival. Extensive programmes of activities were run by the Nuffield Department of Clinical Neurosciences and the Department of Experimental Psychology. In addition, the Department of Physiology, Anatomy and Genetics' Zoltan Molnar in collaboration with Colin Blakemore and St John's College put on a holographic presentation 'The Consciousness Field' created by artist Maria Lopez. |
| Type Of Art | Artistic/Creative Exhibition |
| Year Produced | 2018 |
| Impact | The exhibition was very well attended and the general public had the chance to ask questions from researchers and artists. http://www.theconsciousnessfield.com/index.html |
| URL | https://www.dpag.ox.ac.uk/news/the-oxford-science-and-ideas-festival |
| Description | Our work drew attention to the socio-economic factors of ZIKA syndrome. Our results suggest that maternal protein malnutrition increases susceptibility to congenital zika syndrome. Congenital Zika syndrome is associated with maternal protein malnutrition J Barbeito-Andrés, P Pezzuto, LM Higa, AA Dias, JM Vasconcelos, ... Science Advances 6 (2), eaaw6284 Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS. The potential contribution of impaired brain glucose metabolism to congenital Zika syndrome J Gilbert-Jaramillo, P Garcez, W James, Z Molnár, K Clarke Journal of Anatomy 235 (3), 468-480 |
| First Year Of Impact | 2020 |
| Sector | Healthcare |
| Impact Types | Cultural,Societal,Economic,Policy & public services |
| Description | Keynote Lecture for the Turkish Epilepsy Society Meeting (held online), Istanbul March 2021 |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The developing nervous system can't be considered as a smaller version of the adult brain. The mechanisms of childhood epilepsy are very different from the adult, although the prevalence is just as high. In my lecture I emphasised the lack of knowledge of the basic principles of cerebral cortical circuit formation. Without that knowledge is it very difficult to elevate the platform from which we can tackle some of these devastating conditions. |
| URL | https://www.turkepilepsi.org.tr/etkinlikler/12/aylik-bilimsel-toplantilar/218/future-directions-of-n... |
| Description | Senior Founding Member of the University of Oxford Cortex Club |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The Cortex Club connects researchers at the University of Oxford with world-leading neuroscientists through a unique educational forum dealing with cutting-edge topics and significant challenges in neuroscience. Our events range from small intense debates with up-and-coming scientists to large discussion sessions led by internationally prominent speakers, followed by the opportunity to ask them questions over drinks. News release on the establishment of the cortex club: https://www.dpag.ox.ac.uk/news/cortex-club-celebrates-10-years-of-student-run-talks-and-discussions-for-oxfords-neuroscience-community |
| URL | http://cortexclub.com |
| Description | Symposium speaker on 40th Annual Scientific Meeting of the Australasian Neuroscience Society, Perth |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | I delivered a lecture as a symposium speaker on 40th Annual Scientific Meeting of the Australasian Neuroscience Society, Perth, Australia (online). |
| URL | https://www.ans.org.au/ans-2020-asm/ans-conference |
| Description | Zika virus workshop hosted by the Wellcome Trust, MRC and DIFD discussed rapid response funding, research findings and future policy |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Description | Oxford Martin School Program Grant - 3D Printing for Brain Repair |
| Amount | £1,000,000 (GBP) |
| Organisation | University of Oxford |
| Department | Oxford Martin School |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2020 |
| End | 09/2024 |
| Description | St John's College Research Centre Project Grant |
| Amount | £90,000 (GBP) |
| Organisation | University of Oxford |
| Department | St John's College Oxford |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2017 |
| End | 01/2019 |
| Description | St John's College, Oxford Research Grant |
| Amount | £18,000 (GBP) |
| Funding ID | AVR02540 |
| Organisation | University of Oxford |
| Department | St John's College Oxford |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2020 |
| End | 09/2022 |
| Title | 3D Printing for Brain Repair |
| Description | Oxford Martin School Program on 3D Printing for Brain Repair. A team of Oxford University scientists, comprising DPAG's Zoltán Molnár and Francis Szele, the Department of Chemistry's Hagan Bayley and Oxford Martin Fellow Dr Linna Zhou, are proposing a radical new approach funded by the Oxford Martin School: repairing the brain with 3D-printed neural tissues that are generated from human stem cells. Read the interview with Prof Szele and Molnár on DPAG News. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | https://www.dpag.ox.ac.uk/news/3d-printing-for-brain-repair An in-depth look into a collaborative DPAG, Chemistry and Oxford Martin School project pioneering a radical new approach in which the brain is repaired with 3D-printed neural tissues. Brain damage through injury or disease is devastating for the patient, their families and society. Furthermore, the global economic consequences are known to be expanding exponentially; Alzheimer's Disease alone is projected to affect 92 million people by 2050 when the costs associated with dementia could reach $1.1 trillion a year. So far, existing pharmaceutical and biotherapeutic treatments have been insufficient and clinical trials have repeatedly failed. A team of Oxford University scientists, comprising DPAG's Zoltán Molnár and Francis Szele, the Department of Chemistry's Hagan Bayley and Oxford Martin Fellow Dr Linna Zhou, are proposing a radical new approach funded by the Oxford Martin School: repairing the brain with 3D-printed neural tissues that are generated from human stem cells. Through printing a variety of cortical neurons and supporting glial and endothelial cells, the team will develop layered 'pre-organised' printed neural tissue in vitro that will mimic the basic structure of cerebral cortex columns. They will then transplant the printed layered cortical tissue into animal models of traumatic brain injury initially, a condition which affects 5.3 million people globally. |
| URL | https://www.dpag.ox.ac.uk/news/3d-printing-for-brain-repair |
| Description | Collaboration with King's College London and Federal University of Rio de Janeiro |
| Organisation | Federal University of Sao Carlos |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | The proposed project is a collaborative effort between King's College, London (Dr Helen Stolp) and Federal University of Rio de Janeiro (Dr Patricia Garcez). I hosted both researchers in my laboratory for the analysis of the Brazilian Zika Virus (BrZIKV) infected embryonic and early postnatal mouse brains. We made excellent progress with the project (abstract pasted below). We presented our work on several forums (Wellcome - MRC Zika Forum; Green Templeton College, Oxford Meeting). |
| Collaborator Contribution | ZIKA VIRUS ALTERS PROLIFERATION OF CORTICAL PROGENITORS AND IMPAIRS CORTICAL BLOOD VESSEL DEVELOPMENT IN A CONGENITAL MOUSE MODEL Garcez, PP.1,2, Stolp, HB. 2,3, Sravanam, S. 2, Dias, AA4, Drumond, J. 1, Higa LM. 5, Christoff, RR. 1, Hoerder- Suabedissen, A.2, Victorino, C. 6, Tovar-Moll, F. 1,6,7, Bellio, M. 4, Tanuri, A.5, Lent, R. 1, Molnár, Z.2 1Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 2 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; 3 Centre for the Developing Brain Department of Perinatal Imaging & Health, King's College London, London, UK; 4 Microbiology Institute Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 5 Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 6 National Center for Structural Biology and Biomaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 7D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. Author contributions statement: P.P.G. and H.S. conceived and planned the experiments. D.A.A., J.D. and R.R.C. performed infection experiments. S.S., A.H, H.S., and P.P.G. processed the samples, acquired images and analyzed the data; L.M.H. amplified and titrated ZIKV; M.B., A.T., R.L., Z.M coordinated collaboration, recruitment and provided the laboratory structure and reagents. All authors discussed the results and contributed intellectually to the project. |
| Impact | ZIKA VIRUS ALTERS PROLIFERATION OF CORTICAL PROGENITORS AND IMPAIRS CORTICAL BLOOD VESSEL DEVELOPMENT IN A CONGENITAL MOUSE MODEL Garcez, PP.1,2, Stolp, HB. 2,3, Sravanam, S. 2, Dias, AA4, Drumond, J. 1, Higa LM. 5, Christoff, RR. 1, Hoerder- Suabedissen, A.2, Victorino, C. 6, Tovar-Moll, F. 1,6,7, Bellio, M. 4, Tanuri, A.5, Lent, R. 1, Molnár, Z.2 1Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 2 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; 3 Centre for the Developing Brain Department of Perinatal Imaging & Health, King's College London, London, UK; 4 Microbiology Institute Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 5 Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 6 National Center for Structural Biology and Biomaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 7D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. Microcephaly is strongly linked with Zika virus (ZIKV) infection in humans. ZIKV infects human neural progenitors and impairs the growth of 3D differentiating cultures, such as neurospheres and brain organoids. Moreover, in vitro, ZIKV induces apoptosis in neural progenitors and alters their cell cycle. We established a congenital ZIKV syndrome murine model to further study the cellular and molecular mechanisms of ZIKV infection and brain growth impairment. We also investigated the effect of ZIKV on the different cortical progenitor populations in the interferon gamma (INF?) knockout mice strain. ZIKV injection was performed intravenously in the dam at embryonic day (E) 12.5, and the embryos collected at three days post-infection at E15.5 or as pups at postnatal day (P)2. Adult females presented a loss of weight after ZIKV infection. At E15.5 there was no difference in weight or size of the body or head of the embryos; however, at P2, we observed reduced brain size and reduced weight in comparison to mock-infected animals. Histopathological study revealed that the mitotic index was significantly reduced amongst the apical progenitors. Activated caspase-3 immunoreactivity suggests a discrete increase of dying cells in different telencephalic regions such as the midline and the cortico-striatal boundary. Interestingly, microglia was co-stained with caspase-3 and in the surrounding of the dying cells, suggesting that cell death and microglia could also contribute to apical progenitor reduction. Lipoxin A4 (ALX) receptors that have been implicated in the ability of ZIKV to infect neuroprogenitors are also expressed in brain endothelial cells. We used isolectin B4 (IB4) histochemistry to investigate the blood vessel morphology. Using confocal 3D imaging, we quantified different vasculature parameters such as branching, angiogenic sprouting and vasculature caliber in the ZIKV-infected sections compared to mocks at the embryonic stage of E15 and P2. We found that ZIKV infected brains displayed a reduction in the vascular diameter and had a more immature pattern in comparison to the mock experiments. Vascular defects not only represent a limitation for brain growth and vulnerability, but could also impact on neurogenesis by altering the embryonic vascular niche and signalling to progenitors. Our study suggests that ZIKV could promote microcephaly by inducing cell death in addition to altering the cleavage plane of apical progenitors. ZIKV infection causes direct angiogenetic defects that also contribute to the developmental abnormalities. Author contributions statement: P.P.G. and H.S. conceived and planned the experiments. D.A.A., J.D. and R.R.C. performed infection experiments. S.S., A.H, H.S., and P.P.G. processed the samples, acquired images and analyzed the data; L.M.H. amplified and titrated ZIKV; M.B., A.T., R.L., Z.M coordinated collaboration, recruitment and provided the laboratory structure and reagents. All authors discussed the results and contributed intellectually to the project. Acknowledgments: The authors thank technical support of Fausto Leite. Supported by MRC Rapid Response Grant: Cellular mechanisms of microcephaly due to Zika virus infection in mice to ZM, HS, PPG, RL, FT-M. We also contributed to a brief review papers on ZIKV: Zoltan Molnar and Stephen Kennedy. Neurodevelopmental disorders: Risks of Zika virus during the first trimester of pregnancy. Nature Reviews Neurology 12, 315-316 (2016) |
| Start Year | 2016 |
| Description | BBC Radio Interview - Science in Action about Zika virus |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Radio interview to the BBC program Science in Action about our research that shows that the Zika virus can significantly damage the developing brain. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.bbc.co.uk/programmes/p03q84qx |
| Description | BBC interview |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview about the mosquito-borne Zika virus effects, more dangerous than previously expected. Patricia Garcez have told the BBC that Zika could be behind more damaging neurological conditions, affecting one in five pregnant women who contract it. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.bbc.com/news/world-latin-america-36184799 |
| Description | Brain Diaries Exhibition - Museum of Natural History, University of Oxford |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Extract from the introduction from the exhibition website: Baby, child, teenager, adult Throughout your life, your brain undergoes extraordinary changes. Fascinating physical developments in your brain unlock each new chapter as you grow. And with billions of neurons and trillions of connections, it responds to your experiences to make you the person you are. What does the latest research tell us about how our brains work, from the minute we are conceived to the moment we die? Explore the Brain Diaries to find out....http://www.oum.ox.ac.uk/braindiaries/ |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.oum.ox.ac.uk/braindiaries/ |
| Description | Evolution of the Brain Masterclass - Museum of Natural History, Oxford |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Using the Museum's collections neuroscientist Professor Zoltán Molnár and his laboratory members (https://www.dpag.ox.ac.uk/research/molnar-group) and his medical students from St John's College will lead you through the amazing development and adaptations of the vertebrate brain. |
| Year(s) Of Engagement Activity | 2017,2018 |
| URL | https://www.facebook.com/pg/molnarlab/photos/?tab=album&album_id=730283630497690 |
| Description | Inside Neuroscience: Understanding Zika Virus - A press conference at the Society for Neuroscience |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Around 40 journalists gather in the Society for Neuroscience in San Diego to discuss the latest advances in Zika virus and Microcephaly research. I was in a panel together with three more researchers from the United States, and we have a press office presentation as well as answered the press questions. The media interview and presentations were also broadcasted live. The report was published afterwards in the website: https://www.sfn.org/News-and-Calendar/Neuroscience-Quarterly/Winter-2017/Inside-Neuroscience |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://www.sfn.org/News-and-Calendar/Neuroscience-Quarterly/Winter-2017/Inside-Neuroscience |
| Description | Interview for Nature Medicine Journal |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Nature Medicine Journal Interview about our research in animal models to study whether Zika causes birth defects. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.nature.com/nm/journal/v22/n3/full/nm0316-225.html |
| Description | Interview for Science Magazine |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview for Science Magazine about the effects of Zika virus in brain cells. In particular, it cites our preprint information about how the virus impairs the brain organoid growth. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.sciencemag.org/news/2016/03/zika-virus-kills-developing-brain-cells |
| Description | Interview for Wired magazine |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview about the possible link between Zika virus outbreak and Microcephaly raising numbers in Brazil. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://www.wired.com/2016/02/the-zika-epidemic-is-real-a-link-to-birth-defects-may-not-be/ |
| Description | Interview to the OX Magazine on Brain Awareness Week 2017 |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | From the 10th March the Museum of Natural History are opening an exhibition and series of events on the mysteries of neurological development - Brain Diaries. I was approached by the OX Magazine to give an interview and discuss the highlights of this exhibition and also my own research. This was produced for the general public in Oxfordshire. The interview can be accessed on: http://oxhc.co.uk/Brain-Diaries-In-conversation-with-Professor-Zoltan-Molnar.asp |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://oxhc.co.uk/Brain-Diaries-In-conversation-with-Professor-Zoltan-Molnar.asp |
| Description | Lecture for the Oxford Medical Lecture Club on 28th January 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oxford Medical Lecture Club is for the Retired Clinical Professionals of University of Oxford. The members organise the meetings and invite lecturers. My lecture was on the History of Neuroscience in Oxford (with special attention to Willis and Sherrington). https://www.facebook.com/molnarlab/posts/768407353351984 The members of the group were encouraged to contribute to the History of Medical Sciences Project website with their memories and conserve historic letters, manuscripts with general importance. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.facebook.com/molnarlab/posts/768407353351984 |
| Description | Molnar Laboratory FaceBook Page with over 200 followers |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | The Molnar Laboratory has its own Facebook page: https://www.facebook.com/molnarlab/ There are over 200 followers. The FB page advertises seminars, lectures, conferences and keeps in touch with alumni of the laboratory. |
| Year(s) Of Engagement Activity | 2015,2016,2017,2018,2019 |
| URL | https://www.facebook.com/molnarlab/ |
| Description | Molnar Laboratory Public Facebook Page |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | The Molnar Laboratory's Facebook Page (https://www.facebook.com/molnarlab/) announces relevant seminars, publications, news releases to the audience that follows our activities (around 200 individuals at the moment). |
| Year(s) Of Engagement Activity | 2015,2016,2017,2018 |
| URL | https://www.facebook.com/molnarlab/ |
| Description | Patricia Garcez Public Twitter and Instagram account |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | The twitter and instagram account is ppgarcez. The twitter account has 234 followers and the posts are about public communication, comments about new research about Zika virus and Microcephaly as well as other infectious disease. The instagram has 232 followers and the stories are used to show the daily routine of neuroscience and infectious disease laboratory. |
| Year(s) Of Engagement Activity | 2016,2017,2018 |
| URL | https://twitter.com/ppgarcez |
| Description | Professor Molnar has a Twitter Account with Science Focus |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Professor Molnar has a Twitter Account (https://twitter.com/ZoltanMolnar64) that has outreach function. Seminars, lectures and conferences are advertised. It also draws attention to recent publications and presentations. There are over 300 followers. |
| Year(s) Of Engagement Activity | 2015,2016,2017,2018,2019,2020 |
| URL | https://twitter.com/ZoltanMolnar64 |
| Description | Professor Zoltán Molnár features in BBC programme 'How the NHS Changed our World' |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | https://www.dpag.ox.ac.uk/news/professor-zoltan-molnar-features-in-bbc-programme-how-the-nhs-changed-our-world The BBC recently visited Zoltán Molnár, Professor of Neuroscience here in DPAG, to discuss the research undertaken by Sir Charles Scott Sherrington, during his time in the Laboratory of Physiology, as part of a new series on 'How the NHS Changed our World'. Sherrintgon kept hundreds of of microscope slides in a specially constructed Histological Box, which has been preserved and is now kept by Zoltán here in the Department. In the interview, Zoltán sheds light on how Sherrington and his colleagues would shed their skin for the sake of scientific research. Sherrington's notes reveal how popular self-experimentation was in those days. The interview can be viewed here and you can also watch the whole episode on iPlayer. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.dpag.ox.ac.uk/news/professor-zoltan-molnar-features-in-bbc-programme-how-the-nhs-changed... |
| Description | Quatercentenary of Thomas Willis's birth - Website with Interviews |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Prepared by Department of Physiology, Anatomy and Genetics, St John's College and Oxford Neuroscience, Anatomical Society to celebrate the 400th anniversary of Thomas Willis' birthday on the 27th January 2021. Interviews: Erica Charters, Alastair Buchan, Alastair Compston, Chrystalina Antoniades, Kevin Talbot, Milos Judas, Petra Hofmann, Iain Pears. Lectures and Videos: Prof Alastair Compston - "Dr Thomas Willis's works: 'the most learned Christopher Wren and the inward dens of the Brain" (16th June 2011), Stuart Panter - Thomas Willis' Works Rooms at Oxford, Zoltán Molnár - Opening of the European University for Brain and Technology - Neurotech EU, 16 Dec 2020, Zoltán Molnár - Thomas Willis (1621-1675) 400th Anniversary Lecture, Anatomical Society Winter Meeting, 8th January 2021, Online exhibition at St John's College (opened on 12 January 2021). https://sway.office.com/sDxoxop8O0u4gRD3?ref=Link Prepared by Department of Physiology, Anatomy and Genetics, St John's College, Oxford Neuroscience, and The Anatomical Society to celebrate the 400th anniversary of the birthday of the greatest neuroanatomist of all time, Thomas Willis, on 27 January 2021. |
| Year(s) Of Engagement Activity | 2020,2021 |
| URL | https://www.dpag.ox.ac.uk/about-us/our-history/thomas-willis |
| Description | School Visit (Rio de Janeiro) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | This debate about Zika virus and Microcephaly took place in school located in Rio de Janeiro, in a Zika virus endemic area (Escola Municipal Jose Bonifacio, Sao Joao de Meriti, Rio de Janeiro, Brazil). There were 32 students, age 14-17 years old. The students were very engaged in the activity, discussing about the advances of how Zika virus causes brain malformation, what is the life cycle of the disease vector, Aedes aegypti, and how it was possible to prevent the reproduction of mosquitos at home. The school reported a great interest in having more debates and talk from our University. Since then, other researchers visited the school. This is part of a public engagement programme called "UFRJ doa uma aula" (University of Rio donates a lecture). |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.ufrjdoaumaaula.com.br/cardapio.php |
| Description | The 2015 Brain Awareness Week Lecture at Museum of the History of Science, Oxford 19th March 2015 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The lecture was hosted by the History of Science Museum and it was entitled: "Neuroscience in Oxford: Four Centuries of Discovery". The lecture theatre was completely full and the lecture was recorded and posted to: https://history.medsci.ox.ac.uk/seminars/history-of-medical-sciences-seminar-series/prof-zoltan-molnar-neuroscience-in-oxford-four-centuries-of-discovery/ |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://history.medsci.ox.ac.uk/seminars/history-of-medical-sciences-seminar-series/prof-zoltan-moln... |
| Description | The 2015 Brain Awareness Week Lecture at Museum of the History of Science, Oxford 19th March 2015 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The 2015 Brain Awareness Week Lecture at Museum of the History of Science, Oxford 19th March 2015. This lecture was part of the Brain Awareness Week activities at Oxford. The lecture was entitled: "Neuroscience in Oxford: Four Centuries of Discovery" and was aimed at the general public. The lecture was recorded and now available on: https://history.medsci.ox.ac.uk/seminars/history-of-medical-sciences-seminar-series/prof-zoltan-molnar-neuroscience-in-oxford-four-centuries-of-discovery/ |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://history.medsci.ox.ac.uk/seminars/history-of-medical-sciences-seminar-series/prof-zoltan-moln... |
| Description | Zoltan Molnar organised two workshops on the neurobiology of taste and smell (St John's College and in Department of Physiology, Anatomy and Genetics) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The Workshop started with a scientific preseantation on taste and smell by Professor Laura Lopez-Mascaraque. The talk was aimed to the general public. Then the attendees (30-40 on both occasions) had the opportunity to determine the number of their taste buds after staining the tip of their tongue with food colourant and then exploring the small fungiform papillae within a small selected area with magnifying glasses. Non-tasters have less then 8 buds, average tasters have 8-13 buds, whereas super-tasters have more than 18 buds in a unit area. The participants also tested their olfactory threshold by exploring their sensitivity to capture the odours at different concentrations. Olfactory threshold of a given compound is the minimum odour concentration that is perceived by the human sense of smell. This allows the detection of the different sensitivity degree to capture the odours at different concentrations. Mirror image molecules (known as stereoisomers) have very different smells. The best-known stereoisomers that evoke very different aromas are D-carvone and L-carvone, which smell like caraway and spearmint, respectively. The olfactory discrimination tests proved to be the most challenging tasks of the day. The participants were given 12 different small boxes with different natural aromas. Based on their previous experience they had to name these odours. Participants noted that they "knew what the aromas were" but that they just could not name them. Once the correct responses were announced, the participants could retrospectively identify the aromas of lemon, chocolate, rose etc. The participants also tested their olfactory memory by recognising the hidden aromas in different small boxes, but this test was made easier using small images of three possibilities. This screening test of olfaction is reliable in recognising people with normal olfaction and can distinguish them from people with hyposmia or anosmia. A person with a score of 7 or 8 has a 99.74% probability of having a normal olfaction whereas patients with subjective hyposmia or anosmia score between 0 and 6. The workshop finished with wine tasting demonstrations by the current captain of the Oxford University Blind Tasting Society (Domen Presern and Janice Wang). https://www.dpag.ox.ac.uk/news/worlds-of-sense; https://www.sjc.ox.ac.uk/discover/news/smell-research |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.dpag.ox.ac.uk/news/worlds-of-sense |
| Description | Zoltán Molnár - Opening Lecture for the European University for Brain and Technology - Neurotech EU, 16 Dec 2020 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Prof. Molnar is best known for his careful, insightful and mechanistic studies on brain development across species. He is also an expert in the History of Neuroscience. Therefore we are delighted that he could deliver this lecture on some of the early building blocks of modern neuroscience. As we are opening a new chapter in Brain research and education with our European University, it is a perfect opportunity to look into the past altogether. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.youtube.com/watch?v=5K0r-hjVCBM |
| Description | Zoltán Molnár - Thomas Willis (1621-1675) 400th Anniversary Lecture, Anatomical Society Winter Meeting, |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Zoltán Molnár - Thomas Willis (1621-1675) 400th Anniversary Lecture, Anatomical Society Winter Meeting, |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.youtube.com/watch?v=lJJoWSyn0Zk |