Cell and Developmental Biology


CDB News

A Mexican cave fish may offer heart repair clues

A tiny Mexican fish that can repair its own heart may provide the key to regenerating human heart tissue, according to new research from CDB's Dr Yoshiyuki Yamamoto and colleagues at the University of Oxford.

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New cell movement process key to understanding facial malformations published in Science

The embryonic stem cells that form facial features, called neural crest cells, use an unexpected mechanism of moving from the back of the head to the front to populate the face, finds a new UCL-led study.
The researchers say their findings could help understand how facial defects form, bringing scientists one step closer to repairing craniofacial malformations in the embryo.

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CDB's Vilaiwan Fernandes receives a Wellcome-Beit Prize

We are pleased to report Dr Vilaiwan Fernandes (research profile) was awarded a Wellcome-Beit Prize of £25,000 for her research "Exploring glial roles in sculpting brain development ".
This prize is awarded to promising fellows in additional recognition of their success in obtaining a Wellcome Trust Fellowship to enable them to develop into independent researchers and leaders in their chosen fields.

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The Duchen lab round-up of recent successes

Congratulations to Professor Michael Duchen and his team of researchers for a recent award from the Michael J Fox Foundation. The award of $249,000 over 2 years will support a project which will look into the roles of mitochondrial autophagy in models of Parkinson's Disease.
In addition, the lab has recently been awarded £197,050 by the capital equipment fund to buy new equipment for the Laboratory for Mitochondrial and Metabolic Research. Funds will be used to purchase a 96 well Seahorse respirometry system, a Clariostar fluorescence/luminescence/absorbance plate reader and the CubiAn metabolic analyser. Once these are installed they will be accessible and managed as a core facility. The Laboratory for Mitochondrial and Metabolic Research is a facility supporting the UCL Consortium for Mitochondrial Research.

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CDB’s Caswell Barry awarded over £1.5M Fellowship

Congratulations to Dr Caswell Barry for his successful application for a Wellcome Senior Research Fellowship. The award will be used to support an exciting new project entitled “‘Non-local computations in hippocampal circuits: neural mechanisms” which will aim to study neural mechanisms that underpin memory consolidation and spatial planning.

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Congratulations to Dr Thomas Blacker, the winner of the CNT Early Career Prize

We are very pleased to announce that Dr Thomas Blacker has been awarded the Early Career Prize by the UCL Centre for Neuroimaging Techniques (CNT).
Tom is a BBSRC funded postdoctoral researcher working in Professor Michael Duchen’s lab (Department of Cell and Developmental Biology) in a collaboration with Dr Angus Bain in the Department of Physics and Astronomy.
Please join us in congratulating Tom for his magnificent achievement!
Read more about the UCL Centre for Neuroimaging Techniques Annual Early Career Prize and this year’s winner.

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Congratulations to Professor Susan Evans and Dr Wendy Birch

Please join us in congratulating Professor Susan Evans and Dr Wendy Birch who have been awarded the Anatomical Society Undergraduate Student Summer Research Scholarships.
Adam Ismail - BSc (Intercal) Medical Sciences with Medical Physics and Bioengineering - will be working along Professor Evans (CDB) and Dr Sergio Bertazzo (Medical Physics/BioEngineering) on a project entitled: "Examining the regeneration of mineralised tissue in Tarentola genus geckos".
Sophie Gray - BSc Human Sciences - will join Dr Birch and focus on a project entitled: "Investigation of osteon variation throughout the human body and the impact of this variation on age estimation in a forensic context".
The Society was particularly pleased to be able to award this year thirteen scholarships which highlights the outstanding quality of the applications received.

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Congratulations to CDB’s Professor Michael Duchen, winner of the 2018 Charles L. Hoppel Prize for Outstanding Contributions in Mitochondrial Research

The prize is supported by an endowment that was established to honor Professor Hoppel’s service to Case Western Reserve University School of Medicine and his distinguished career in mitochondrial biology as a researcher, educator and mentor.
Professor Duchen was selected from a highly competitive pool of nominees based on the recognition of his contributions as an innovative pioneer and world leader in mitochondrial physiology. Moreover, his commitment to students and colleagues and his continued service to the broader community reflect the values that Charles Hoppel has displayed over his 50-year career as an academic scientist.
Professor Duchen will receive the Prize on the occasion of presenting the second annual Charles L. Hoppel Lecture in the autumn of 2018 at Case Western Reserve University School of Medicine, where he will describe the research leading to his current investigations.

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Artificial muscles study led by the Tedesco lab promise to speed up testing of treatments for muscular dystrophies

The study, published in Cell Reports, found that 3D artificial muscles can be generated from both healthy and diseased stem cells of patients with different types of severe muscle disorders. The artificial muscles accurately model severe genetic muscle diseases, which will allow scientists to test different types of therapies on human cells that embody the characteristics of the patients.

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Latest papers published by the Evans Lab

"The first record of albanerpetontid amphibians (Amphibia: Albanerpetontidae) from East Asia"
Abstract: Albanerpetontids are an enigmatic fossil amphibian group known from deposits of Middle Jurassic to Pliocene age. The oldest and youngest records are from Europe, but the group appeared in North America in the late Early Cretaceous and radiated there during the Late Cretaceous. Until now, the Asian record has been limited to fragmentary specimens from the Late Cretaceous of Uzbekistan. This led to speculation that albanerpetontids migrated into eastern Asia from North America in the Albian to Cenomanian interval via the Beringian land bridge. However, here we describe albanerpetontid specimens from the Lower Cretaceous Kuwajima Formation of Japan, a record that predates their first known occurrence in North America. One specimen, an association of skull and postcranial bones from a single small individual, permits the diagnosis of a new taxon. High Resolution X-ray Computed Microtomography has revealed previously unrecorded features of albanerpetontid skull morphology in three dimensions, including the presence of a supraoccipital and epipterygoids, neither of which occurs in any known lissamphibian. The placement of this new taxon within the current phylogenetic framework for Albanerpetontidae is complicated by a limited overlap of comparable elements, most notably the non-preservation of the premaxillae in the Japanese taxon. Nonetheless, phylogenetic analysis places the new taxon closer to Albanerpeton than to Anoualerpeton, Celtedens, or Wesserpeton, although Bootstrap support values are weak. The results also question the monophyly of Albanerpeton as currently defined.

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New paper from Claudio Stern’s lab in PNAS: “Neural induction by the node and placode induction by head mesoderm share an initial state resembling neural plate border and ES cells”

During development, various organ systems are set aside from the rest of the embryo as a result of “induction” from specific signalling tissues, called organizers. This paper reveals that inductions of the nervous system and of cranial sensory placodes, by different organizers, begin by the same step, which resembles the pluripotent state of embryonic stem cells. This suggests that the first event in specifying organ systems is an “erasure” of information that reverts cells back to an earlier developmental state before redirecting them to their final fate.

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"Gender equality from a European perspective: myth and reality" - new paper by Professor Patricia Salinas (CDB) published in Neuron

In the past 50 years, significant progress in women’s equality has been made worldwide. Western countries, particularly European countries, have implemented initiatives to attain a more gender-balanced workforce with the introduction of family friendly policies, by trying to narrow the gender pay gap and by promoting women’s career progression. In academia, however, fewer women reach top leadership positions than those in the political arena. These findings suggest that academia needs to carefully evaluate why these new policies have not been very effective. In this article, we report on the progress made in higher education, the shortcomings, and how new initiatives hold great promise for improving gender equality in academia around the globe.

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A novel strategy for ex vivo gene therapy using artificial chromosomes in human muscle stem cells published by CDB's Francesco Saverio Tedesco and colleagues in EMBO Molecular Medicine

In this new study Sara Benedetti et al. have shown that reversible immortalisation of human dystrophic muscle progenitor cells enables their genetic correction with novel human artificial chromosomes (HACs) containing the entire dystrophin genetic locus, providing evidence of translation of HAC technology for ex vivo gene therapy of Duchenne muscular dystrophy. The authors have first used lentiviral vectors to deliver specific genes to extend proliferation of different types of human skeletal muscle progenitor cells. Importantly, they have also made this process reversible. The extension of the proliferative ability of muscle cells derived from patients with Duchenne muscular dystrophy allowed their genetic correction with a novel HAC. Finally, this strategy enabled the development of a next‐generation, multifunctional HAC containing several different genes, which could be one of the largest and most complex gene therapy vectors developed to date. This exciting study has been developed in collaboration with scientists at the University of Manchester, University of Milan (Italy) and Tottori University (Japan).

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Evans Lab round-up

The Evans lab welcomes a new PhD student from Mexico - Ivan Rodrigo Reyes Perez. Ivan, who has successfully obtained a CONACyT studentship from the Mexican government, will be working with Professor Evans and Dr Yamamoto on eye and skull development.

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2 new papers co-authored by CDB's Dr Gerold Baier published by Frontiers in Computational Neuroscience and Network Neuroscience

Electro-cortical activity in patients with epilepsy may show abnormal rhythmic transients in response to stimulation. Even when using the same stimulation parameters in the same patient, wide variability in the duration of transient response has been reported. These transients have long been considered important for the mapping of the excitability levels in the epileptic brain but their dynamic mechanism is still not well understood. To investigate the occurrence of abnormal transients dynamically, we use a thalamo-cortical neural population model of epileptic spike-wave activity and study the interaction between slow and fast subsystems. In a reduced version of the thalamo-cortical model, slow wave oscillations arise from a fold of cycles (FoC) bifurcation. This marks the onset of a region of bistability between a high amplitude oscillatory rhythm and the background state. In vicinity of the bistability in parameter space, the model has excitable dynamics, showing prolonged rhythmic transients in response to suprathreshold pulse stimulation. We analyse the state space geometry of the bistable and excitable states, and find that the rhythmic transient arises when the impending FoC bifurcation deforms the state space and creates an area of locally reduced attraction to the fixed point. This area essentially allows trajectories to dwell there before escaping to the stable steady state, thus creating rhythmic transients. In the full thalamo-cortical model, we find a similar FoC bifurcation structure. Based on the analysis, we propose an explanation of why stimulation induced epileptiform activity may vary between trials, and predict how the variability could be related to ongoing oscillatory background activity. We compare our dynamic mechanism with other mechanisms (such as a slow parameter change) to generate excitable transients, and we discuss the proposed excitability mechanism in the context of stimulation responses in the epileptic cortex.

Read full paper: Understanding epileptiform after-discharges as rhythmic oscillatory transients
Authors: Gerold Baier, Peter N. Taylor and Yujiang Wang

Electroencephalography (EEG) allows recording of cortical activity at high temporal resolution. EEG recordings can be summarised along different dimensions using network-level quantitative measures, e.g. channel-to-channel correlation, or band power distributions across channels. These reveal network patterns that unfold over a range of different time scales and can be tracked dynamically.
Here we describe the dynamics of network-state transitions in EEG recordings of spontaneous brain activity in normally developing infants and infants with severe early infantile epileptic encephalopathies (n=8, age: 1-8 months). We describe differences in measures of EEG dynamics derived from band power, and correlation-based summaries of network-wide brain activity.
We further show that EEGs from different patient groups and controls may be distinguishable based on a small set of the novel quantitative measures introduced here, which describe dynamic network state switching. Quantitative measures related to the sharpness of switching from one correlation pattern to another show the largest differences between groups.
These findings reveal that the early epileptic encephalopathies are associated with characteristic dynamic features at the network level. Quantitative network-based analyses like the one presented here may in future inform the clinical use of quantitative EEG for diagnosis.

Read full paper: Network dynamics in the healthy and epileptic developing brain
Authors:  RE Rosch, T Baldeweg, F Moeller and G Baier

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The Crick: Bringing Biomedical Research To Life!

This Student Selected Component (SSC) for 1st year medical students was set up this year by Drs Faye Gishen (NHS consultant physician at the Royal Free Hospital) and Gregor Campbell (Department of Cell & Developmental Biology) with the assistance of Dr Hazel Smith, the Faculty of Life Sciences (FLS) Faculty Tutor and teaching officers at the Francis Crick Institute.

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New paper by H. Freyja Ólafsdóttir, Francis Carpenter and Caswell Barry

H. Freyja Ólafsdóttir, Francis Carpenter and Caswell Barry, "Task Demands Predict a Dynamic Switch in the Content of Awake Hippocampal Replay" will be published in Neuron on Thursday 19 October 2017, 5pm UK time / 12pm US Eastern time and is under a strict embargo until this time.

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Neanderthal growth patterns revealed

Ontogenetic studies help us understand the processes of evolutionary change but no one single system defines the ontogeny of an individual. Previous studies of Neanderthals have focused more on the pace than the pattern of growth. Thirteen genetically related Neanderthals have been recovered from the 49 ky site of El Sidrón, Asturias, Spain, including a new juvenile partial skeleton for which there is associated dental, cranial and postcranial material.

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Fossil skull sheds light on ape ancestry

A remarkably complete fossil skull discovered in Kenya reveals what the common ancestor of all living apes and humans may have looked like, according to a new study involving UCL research.
The find, announced today in Nature, belongs to an infant that lived about 13 million years ago. It’s a significant discovery that will help researchers uncover whether the common ancestor of living apes and humans originated in Africa and what these early ancestors looked like.
The study involved a large international team including Professor Fred Spoor at UCL and was led by Professor Isaiah Nengo of the Turkana Basin Institute, Stony Brook University and De Anza College, USA.

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With great sadness, we announce the death of our esteemed colleague Professor Mitch Glickstein, on March 14th 2017

Professor Glickstein was born in Roxbury, south of Boston, in 1931. He attended different schools in the Boston area and showed the same indifference to nearly all of them, but managed to enter Bucknell University in Pennsylvania and, subsequently, transfer to the University of Chicago. He loved living in Chicago and studying in that great institution known for its academic rigour, diverse student body and lively political culture at a time when McCarthyism was in full swing. Following graduation in 1951, he set off on a great adventure around the world, using commercial ships at sea and various forms of transport on land, to visit England, France, Italy, Greece, Israel, Ceylon, Singapore, Korea and Japan for various lengths of time, before returning to the United States. He returned to the University of Chicago a few years later to begin his postgraduate studies in psychology.
This was a crucial period in his life when he decided that he did not want to be a clinical psychologist, but began to show a keen interest in the study of the brain. Undoubtedly, he was influenced by many of his already renown teachers and associates such as Austin Riesen, Roger Sperry, Ronnie Myers and Garth Thomas amongst others. He followed Roger Sperry to Cal Tech as a Research Fellow upon receiving his PhD in 1958. He found Cal Tech a lively place and Sperry’s lab a fertile ground for neuroscience. It was full of excellent people doing brilliant science either on nerve regeneration or on the function of the corpus callosum; the latter of which became the focus of Mitch’s work during his 2-year stay in the lab. He subsequently moved to Stanford to work with Karl Pribram in 1960-1961.

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New paper from the Patel lab published in Cell Reports identifies Ca2+ as a key regulator of physical junctions between organelles

Endosomes form junctions with the endoplasmic reticulum (ER) but how such proximity is regulated is unclear. The paper by joint first authors Bethan Kilpatrick and Emily Eden shows that release of Ca2+ by an endosomal ion channel facilitates inter-organellar coupling to temper signals mediated by an internalised growth factor. Endosome-ER contact sites thus emerge as Ca2+-dependent signalling hubs.

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CDB's Szabadkai team receives Wellcome Trust Pathfinder Award to study mitochondrial subtypes of breast cancer

Gyorgy Szabadkai (UCL Department of Cell and Developmental Biology) together with Robert Stein (UCLH, UCL Cancer Institute) and Mariia Yuneva (Francis Crick Institute) and Kevin Bryson (UCL Computer Sciences) as CoI, has received a Wellcome Trust Pathfinder Award to develop a mitochondrial gene expression based biomarker to inform on chemosensitivity of luminal breast tumours.

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Professor Steve Hunt delivers prestigious Pat Wall Lecture

Congratulations to Professor Stephen Hunt who delivered the Pat Wall Lecture at the 2016 Annual Scientific Meeting of the British Pain Society.

About the Pat Wall lecture:

An invitation to deliver the British Pain Society’s Annual Pat Wall Lecture at its Annual Scientific Meeting and receive its associated medal is made to a distinguished and outstanding basic scientist.  This lecture is held in honour of Professor Pat Wall (1925-2001). While Professor Wall was working at Massachusetts Institute of Technology he met Ronald Melzack and they published The Gate Control Theory of Pain in 1965.  Pat Wall was also the first editor of the journal Pain.   From 1967-1990 he was Professor of Anatomy at University College London. He also co-edited the first Textbook of Pain in 1983. He was elected a Fellow of The Royal Society in 1989, was awarded the Royal Medal of the Royal Society in 1999.  He had an international reputation for research work on pain, especially the application of basic research for clinical benefit.

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