Seminars

New directions in optical microscopy

21th March 2018.  
W Brad Amos, MRC Laboratory of Molecular Biology, Cambridge              

Abstract 
The fourth seminar of the Light microscopy series will be given by William B Amos of the MRC Laboratory of Molecular Biology in Cambridge in the College lecture theatre on Wednesday the 21st of March at 2.00 pm and will address New directions in optical microscopy. The seminar will cover: Multiphoton microscopy on the one hand and Super-resolution methods on the other.  The latter inclu Optical (structured Illumination) and Photochemical (Stimulated Emission Depletion STED, Stochastic optical reconstruction, STORM and Photoactivation Light Microscopy PALM)discuss standardised distances in compound microscopes, lens aberrations, diffraction in the light microscope, Rayleigh resolution and Fourier synthesis. The poster of the series can be downloaded here.

Biography
William Brad Amos was trained as a zoologist, researched in cell biology and is now a designer of optical instruments. With John White, Mick Fordham and Richard Durbin in Cambridge, he developed an instrument that has set the standard of modern confocal microscopes.  Derivatives of this instrument are now made by many companies and are in use throughout the world. His scientific work is now carried out done in collaboration with Gail McConnell in the University of Strathclyde. This collaboration has resulted in several novel applications of optical physics in microscopy, including what is arguably the greatest design change in microscope objectives  for 100 years. This is called the Mesolens, the name signifying that it has the wide field of a photographic macro lens and the high resolution of a microscope objective. 

 

 

 

 

Polarisation and interference methods

20th March 2018.  
W Brad Amos, MRC Laboratory of Molecular Biology, Cambridge              

Abstract 
The third seminar of the Light microscopy series will be given by William B Amos of the MRC Laboratory of Molecular Biology in Cambridge in the College lecture on Tuesday tthe 20th of March at 2.00 pm and will address Polarisation and Interference Methods. The seminar will discuss the nature of polarised light, the way in which polarised light interacts with crystals and biomolecules, differential interference contrast using polarisation and the use of fluorescence in microscopy including fluorescence correlation spectroscopy, fluorescent lifetime measurements and Forster resonance energy transfer.

Biography
William Brad Amos was trained as a zoologist, researched in cell biology and is now a designer of optical instruments. With John White, Mick Fordham and Richard Durbin in Cambridge, he developed an instrument that has set the standard of modern confocal microscopes.  Derivatives of this instrument are now made by many companies and are in use throughout the world. His scientific work is now carried out done in collaboration with Gail McConnell in the University of Strathclyde. This collaboration has resulted in several novel applications of optical physics in microscopy, including what is arguably the greatest design change in microscope objectives  for 100 years. This is called the Mesolens, the name signifying that it has the wide field of a photographic macro lens and the high resolution of a microscope objective. 

 

 

 

 

Ray and wave optics and practical microscopy

19th March 2018.  
W Brad Amos, MRC Laboratory of Molecular Biology, Cambridge              

Abstract 
The second seminar of the Light microscopy series will be given by William B Amos of the MRC Laboratory of Molecular Biology in Cambridge in the College lecture theatre on Monday the 19th of March at 4.00 pm and will address Ray and wave optics and practical microscopy. The seminar will discuss standardised distances in compound microscopes, lens aberrations, diffraction in the light microscope, Rayleigh resolution and Fourier synthesis. The poster of the series can be downloaded here.

Biography
William Brad Amos was trained as a zoologist, researched in cell biology and is now a designer of optical instruments. With John White, Mick Fordham and Richard Durbin in Cambridge, he developed an instrument that has set the standard of modern confocal microscopes.  Derivatives of this instrument are now made by many companies and are in use throughout the world. His scientific work is now carried out done in collaboration with Gail McConnell in the University of Strathclyde. This collaboration has resulted in several novel applications of optical physics in microscopy, including what is arguably the greatest design change in microscope objectives  for 100 years. This is called the Mesolens, the name signifying that it has the wide field of a photographic macro lens and the high resolution of a microscope objective. 

 

 

 

 

Resolution and the nature of optical images

19th March 2018.  
W Brad Amos, MRC Laboratory of Molecular Biology, Cambridge              

Abstract 
The first seminar of the Light microscopy series will be given by William B Amos of the MRC Laboratory of Molecular Biology in Cambridge on Monday the 19th of March in the College lecture theatre at 2.00 pm and will address Resolution and the nature of optical images. The seminar will discuss the nature of images obtained the light microscope, Abbe's equation for resolution as well as recent developments such Interferometric Fluorescent Superresolution Microscopy (iPALM) and Coherent anti-Stokes Raman Spectroscopy (CARS). The poster of the series can be downloaded here.

Biography
William Brad Amos was trained as a zoologist, researched in cell biology and is now a designer of optical instruments. With John White, Mick Fordham and Richard Durbin in Cambridge, he developed an instrument that has set the standard of modern confocal microscopes.  Derivatives of this instrument are now made by many companies and are in use throughout the world. His scientific work is now carried out done in collaboration with Gail McConnell in the University of Strathclyde. This collaboration has resulted in several novel applications of optical physics in microscopy, including what is arguably the greatest design change in microscope objectives  for 100 years. This is called the Mesolens, the name signifying that it has the wide field of a photographic macro lens and the high resolution of a microscope objective. 

 

 

 

 

From IMAT to BMAT

12th June 2017.  
Tori Helmer, Cambridge Assessment, University of Cambridge               

Abstract 
Several years ago the Italian Ministry entrusted Cambridge Assessment, a Department of the University of Cambridge, with the responsibility of developing a test for admission of prospecive medical students to Italian medical schools offering a course taught in English. The result of this work was the International Medical Admission Test (IMAT), which has been used for several years now asd the sole criterium for admission of prospective medical students to the relevant courses.  In her talk Tori Helmer will review the key features of IMAT and will compare them with those of another admission test - the so called biomedical admission test (BMAT) used in the United Kingdom and in many other countries around the world. The talk will demonstrate that BMAT offers a superior evaluation of candidates and that the test is predictive of future success of the students throughout their future undergraduate course. Thus a transition from IMAT to BMAT would serve prospective and Italian Universities better than the current, IMAT-based, system.

All College students are warmly encouraged to participate. The text of the seminar can be downloaded here

 

 

 

 

From ChIP-Seq to a Role for Tropomyosin-4 in Platelet Biogenesis

10th April 2017.  
Marloes Tijssen, Department of Haematology, University of Cambridge

Abstract 
Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets. Platelet number and volume are independent risk factors for heart attack and stroke. We have identified 2 unrelated families in the BRIDGE Bleeding and Platelet Disorders (BPD) collection who carry a TPM4 variant that causes truncation of the TPM4 protein and segregates with macrothrombocytopenia, a disorder characterized by low platelet count. N-Ethyl-N-nitrosourea-induced (ENU-induced) missense mutations in Tpm4 or targeted inactivation of the Tpm4 locus led to gene dosage-dependent macrothrombocytopenia in mice. All other blood cell counts in Tpm4-deficient mice were normal. Insufficient TPM4 expression in human and mouse megakaryocytes resulted in a defect in the terminal stages of platelet production and had a mild effect on platelet function. Together, our findings demonstrate a nonredundant role for TPM4 in platelet biogenesis in humans and mice and reveal that truncating variants in TPM4 cause a previously undescribed dominant Mendelian platelet disorder.

Biography
Dr Marloes Tijssen is a Research Scientist – Programme Leader at the University of Cambridge. Dr Tijssen graduated from the VU University Amsterdam with an MSc in ‘Medical biology’ and completed her PhD studies at Sanquin Research/University of Amsterdam. In 2008 she moved to the Department of Haematology at the University of Cambridge and secured a prestigious Rubicon Fellowship from the Dutch government and a Marie Curie Intra European Fellowship. In the laboratory of Prof Göttgens she generated a genome-wide catalogue of transcription factor binding in megakaryocytes, the precursors of platelets, leading to the discovery of novel regulators of megakaryopoiesis. She was awarded a European Hematology Fellowship and a British Heart Foundation project grant to further characterise these novel regulators, including Tropomyosin 4 (TPM4). In collaboration with the BRIDGE consortium and Prof Ouwehand’s group they have shown that a mutation in TPM4 causes macrothrombocytopenia.

References
[1]  Pleines I, Woods J, Chappaz S, Kew V, Foad N, Ballester-Beltrán J, Aurbach K, Lincetto C, Lane RM, Schevzov G, Alexander WS, Hilton DJ, Astle WJ, Downes K, Nurden P, Westbury SK, Mumford AD, Obaji SG, Collins PW, Delerue F, Ittner LM, Bryce NS, Holliday M, Lucas CA, Hardeman EC, Ouwehand WH, Gunning PW, Turro E, Tijssen MR, Kile BT. Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia. J Clin Invest. 2017 Mar 1;127(3):814-829.

[2]  Tijssen MR, Cvejic A, Joshi A, Hannah RL, Ferreira R, Forrai A, Bellissimo DC, Oram SH, Smethurst PA, Wilson NK, Wang X, Ottersbach K, Stemple DL, Green AR, Ouwehand WH, Göttgens B. Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev Cell. 2011 May 17;20(5):597-609.

Image: Red blood cells entangled by fibrin. Courtesy of Science Photo Library.

All College students are warmly encouraged to participate. The poster of the seminar can be downloaded here

 

 

 

 

Making Platelets in vitro: an environmental question and making it count.

10th April 2017.  
Cédric Ghevaert, Wellcome Trust - MRC Stem Cell Institute, Cambridge

Abstract 
The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

Biography
After completing his MD at the Universite Libre de Bruxelles (which also included a whole year studying at the University of Bristol, UK) in 1997, Dr Ghevaert started his career training in Internal Medicine in the United Kingdom and became a member of the Royal College of Physicians in 2000. He went on to specialize in Haematology (completing his training in 2005). His intention was always to have an academic career and he therefore started a PhD at the University of Cambridge. He completed his PhD in 2008 and moved on as a post-doctoral clinical fellow to Prof Steve Watson laboratory at the University of Birmingham where he obtained a personal Intermediate Clinical Fellowship from the British Heart Foundation. This programme of research allowed him to further his knowledge of platelet and megakaryocyte biology. In 2010 he obtained a tenure post as Senior Lecturer in Transfusion Medicine in the Department of Haematology at the University of Cambridge where he now runs a research group with a special interest in two main fields of research: 1. production in vitro of blood cells for transfusion in humans using pluripotent stem cells technologies and 2. in vitro modelling of inherited platelet disorders. His research is supported by various funding bodies including NHS Blood and Transplant, the British Heart Foundation, National Institute for Health and Research.

References
[1] Moreau T, Evans AL, Vasquez L, Tijssen MR, Yan Y, Trotter MW, Howard D, Colzani M, Arumugam M, Wu WH, Dalby A, Lampela R, Bouet G, Hobbs CM, Pask DC, Payne H, Ponomaryov T, Brill A, Soranzo N, Ouwehand WH, Pedersen RA, Ghevaert C. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat Commun. 2016 Apr 7;7:11208.

[2] Guerrero JA, Bennett C, van der Weyden L, McKinney H, Chin M, Nurden P, McIntyre Z, Cambridge EL, Estabel J, Wardle-Jones H, Speak AO, Erber WN, Rendon A, Ouwehand WH, Ghevaert C. Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice. Blood. 2014 Dec 4;124(24):3624-35.

Image: A drawing by G Bizzozero describing a platelet rich thrombus. Giulio Bizzozero, although not the first to observe 'blood corpuscles' later known as platelets, was the scientist who defined their role in coagulation adn thrombosis. Original reference: G Bizzozero. Ueber einen neuen Forrnbestandteil des Blutes und dessen Rolle bei der Thrombose
und Blutgerinnung.  Archiv fur pathologische Anatomie und Physiologie und fur klinische Medicin 90: 261–332 (1882)

All College students are warmly encouraged to participate. The poster of the seminar can be downloaded here

 

 

 

 

A Life Passion for Vaccines. How the Vaccines for Pertussis and Meningitis Were Developed.

21th March 2017.  
Mariagrazia Pizza, GSK Vaccines, Siena

Abstract 
Since the beginning of human evolution, approximately 3 million years ago to the mid 1700’s, life expectancy has been between 25 and 35 years. Today is more than 80 years. One of the major contributors in the increase in life expectancy has been the use of vaccines in preventing infectious diseases. However, most of the vaccines available today, although very effective, have been developed at the end of last century using conventional technologies. The vaccinology field is evolving very rapidly, with the modern technologies providing alternative ways in designing improved vaccines or novel vaccines against infections for which preventive measures do not exist. Today is possible to identify new antigens directly from the genome (Reverse Vaccinology), and apply a structure-based design to deliver more stable and more immunogenic antigens (Structural Vaccinology). The Reverse Vaccinology approach has been instrumental for the development of a new vaccine against Neisseria meningitidis serogroup B, a bacterium causing a devastating disease characterized by meningitis and sepsis.

Biography
Mariagrazia Pizza was educated as a pharmaceutical chemist at the University of Naples, Italy. After a fellowship at the EMBL laboratories in Heidelberg, Germany, she moved to Siena, Italy, where she stayed ever since as a scientist and Project leader, responsible for many bacterial projects. During this period, she has contributed to the discovery and licensure of two innovative bacterial vaccines, against pertussis and meningococcus B. She is currently a Discovery Project Leader at the Research and Development Centre of GSK Vaccines, in Siena. During her career, she received many scientific awards. She is co-author of over 180 publications in International peer-reviewed journals and over 150 patents.

All College students are warmly encouraged to participate. The poster of the seminar can be downloaded here

Image: Scanning electron micrograph of N meninigitidis, a bacterium causing meninigitis.

 

 

 

Genome Editing: its Promise for Society and Some Potential Perils

13th March 2017.  
John Parrington University of Oxford

Abstract 
Since the birth of civilisation, human beings have manipulated other life-forms. The ability to directly engineer the genomes of organisms first became possible in the 1970s, when the gene for human insulin was introduced into bacteria to produce this protein for diabetics. At the same time, mice were modified to produce human growth hormone, and grew huge as a result. But these were only our first tottering steps into the possibilities of genetic engineering. In the past few years, the pace of progress has accelerated enormously. We can now cut and paste genes using molecular scissors with astonishing ease, and the new technology of genome editing can be applied to practically any species of plants or animals. These new technologies hold much promise for improving lives. Genome editing may soon be used to treat rare genetic disorders, but also diseases like AIDS, by genetically modifying patients’ white blood cells to be resistant to HIV. In agriculture, genome editing could be used to engineer species with increased food output, and the ability to thrive in challenging climates. But these powerful new techniques also raise important ethical dilemmas and potential dangers, pressing issues that are already upon us given the speed of scientific developments.
To what extent should parents be able to manipulate the genetics of their offspring - and would designer babies be limited to the rich? Can we effectively weigh up the risks from introducing synthetic lifeforms into complex ecosystems? John Parrington explains the nature and possibilities of these new scientific developments, which could usher in a brave, new world. We must rapidly come to understand its implications if we are to direct its huge potential to the good of humanity and the planet.

Biography
John Parrington is an Associate Professor in Molecular and Cellular Pharmacology at the University of Oxford, and a Tutorial Fellow in Medicine at Worcester College, Oxford. He has published over 90 peer-reviewed articles in science journals including Nature, Current Biology, Journal of Cell Biology, Journal of Clinical Investigation, The EMBO Journal, Development, Developmental Biology, and Human Reproduction. He has extensive experience writing popular science, having published articles in The Guardian, New Scientist, Chemistry World, and The Biologist. He has also written science reports for the Wellcome Trust, British Council, and Royal Society. He is the author of The Deeper Genome, (Oxford University Press, 2015) and Redesigning Life (Oxford University Press, 2016).

All College students are warmly encouraged to participate. The poster of the seminar can be downloaded here.

 

 

 

Evolution of Research Assessment in the UK

6th March 2017.  
Steven Hill, Higher Education Funding Council for England

Abstract
Periodic national research assessments of universities have been a feature of the United Kingdom's research policy landscape for more than 3 decades. In this talk I will chart the development and evolution of the approaches to research assessment, focusing on debates about the role of peer review and metrics, and examining the introduction of societal impact assessment in the most recent exercise, the Research Excellence Framework 2014 (REF2014). Finally, I will outline the plans for the next exercise, REF2021, and the current areas of debate and discussion.

Biography
Steven Hill is Head of Research Policy at the Higher Education Funding Council for England. At HEFCE Steven is responsible for research funding and assessment, open research, public engagement and impact. He is the chair of the steering group for the 2021 Research Excellence Framework, that is currently under development. Prior to joining HEFCE Steven was Head of the Strategy Unit at Research Councils UK, and had several roles in the Department for Environment, Food and Rural Affairs, working on evidence-based policy making. Earlier in his career Steven was a university lecturer at the University of Oxford where his research focused on plant biology.

All College students are warmly encouraged to participate. The poster of the seminar can be downloaded here.

Image: A portrait of English natural scientist C Darwin.

 

 

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