Hazel Corradi

University of Bath

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Co-Authors

K. Ravi Acharya

University of Bath

Edward D. Sturrock

University of Cape Town

Sylva L. U. Schwager

University of Cape Town

Anne V. Corrigall

University of Cape Town

B.T. Sewell

University of Cape Town

Ester Boix

Universitat Autònoma de Barcelona

C. Gopi Mohan

Amrita Vishwa Vidyapeetham

R. Natesh

Indian Institute of Science Education and Research Thiruvananthapuram

Jean M. Watermeyer

Institute of Structural and Molecular Biology

Dimitris Georgiadis

National and Kapodistrian University of Athens

Cooperative Institutions

Miyoshi Kasei (Japan)

114

Université d'Angers

112

Avery Dennison (United States)

108

Weatherford College

University of Cape Town

Harvard University

University of Bath

Universidade Federal de São Paulo

Centre National de la Recherche Scientifique

National Institutes of Health

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Building confidence through doing: Support maths for bioscientists

Hazel Corradi Nicola M. Coyle Natalie Ring

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Citations (0)

Crystal Structure of the N Domain of Human Somatic Angiotensin I-converting Enzyme Provides a Structural Basis for Domain-specific Inhibitor Design

Journal of Molecular Biology (2006)

Hazel Corradi Sylva L. U. Schwager Aloysius T. Nchinda Edward D. Sturrock K. Ravi Acharya

Linker

Cooperativity

Lisinopril

10.1016/j.jmb.2006.01.048

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Citations (162)

Structure of Testis ACE Glycosylation Mutants and Evidence for Conserved Domain Movement^,

Biochemistry (2006)

Jean M. Watermeyer B.T. Sewell Sylva L. U. Schwager R. Natesh Hazel Corradi

Human angiotensin-converting enzyme is an important drug target for which little structural information has been available until recent years. The slow progress in obtaining a crystal structure was due to the problem of surface glycosylation, a difficulty that has thus far been overcome by the use of a glucosidase-1 inhibitor in the tissue culture medium. However, the prohibitive cost of these inhibitors and incomplete glucosidase inhibition makes alternative routes to minimizing the N-glycan heterogeneity desirable. Here, glycosylation in the testis isoform (tACE) has been reduced by Asn-Gln point mutations at N-glycosylation sites, and the crystal structures of mutants having two and four intact sites have been solved to 2.0 A and 2.8 A, respectively. Both mutants show close structural identity with the wild-type. A hinge mechanism is proposed for substrate entry into the active cleft, based on homology to human ACE2 at the levels of sequence and flexibility. This is supported by normal-mode analysis that reveals intrinsic flexibility about the active site of tACE. Subdomain II, containing bound chloride and zinc ions, is found to have greater stability than subdomain I in the structures of three ACE homologues. Crystallizable glycosylation mutants open up new possibilities for cocrystallization studies to aid the design of novel ACE inhibitors.

N-linked glycosylation

10.1021/bi061146z

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Citations (54)

Structure of protoporphyrinogen oxidase from Myxococcus xanthus with acifluorfen

Hazel Corradi Anne V. Corrigall Ester Boix C. Gopi Mohan Edward D. Sturrock

Myxococcus xanthus

Protoporphyrinogen oxidase

10.2210/pdb2ivd/pdb

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Citations (0)

Structure of human somatic angiontensin-I converting enzyme N domain

Hazel Corradi Sylva L. U. Schwager A. Nichinda Edward D. Sturrock K. Ravi Acharya

10.2210/pdb2c6f/pdb

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Devising an Online Resource to Help Undergraduate Science Students Critically Evaluate Research Articles

Journal of Academic Writing (2015)

Trevor A. Day Julie Letchford Hazel Corradi Thomas J. Rogers

Critically evaluating research papers is an important vehicle for promoting acculturation into a scientific discipline. As science students progress through their undergraduate studies, their critical abilities are expected to become heightened, and research papers are read and cited in order to support a variety of assignments, such as essays, critical reviews and presentations, progressing to shaping laboratory research projects and dissertation-writing. This article describes the process of designing a modular online resource. The resource is aimed at familiarising students with the structural conventions and argumentative devices used in research papers and supporting them in deep-reading a research paper in life sciences or chemistry. The modules employ audio- and video-recorded extracts from interviews with a key author to provide a context for the origins, motivations and processes behind the writing of a specific paper, plus scaffolded questions to encourage critical evaluation of the paper. Notable features of the project were the employment of a multi-disciplinary team of staff and research postgraduates coupled with the developmental testing of the resource by undergraduates. Lessons learnt from the project are considered, including the resource's integration within the curriculum and the challenges of writing such interactive resources for different disciplines.

Discipline

Argumentative

10.18552/joaw.v5i2.172

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Citations (1)

A sample practical report to facilitate writing in the scientific style

Biochemistry and Molecular Biology Education (2011)

Hazel Corradi

The ability to write concise and accurate scientific reports is highly valued in university level science. The graduate outcomes for bioscience degrees in England include a requirement for students to be able to analyze, critique, present, and discuss original data in their discipline [1] as these are a key part of the skills a professional bioscientist needs. This is consistent with the wide use of “final year projects,” where many finish their degree by taking on their own project, analyzing their own data, and presenting the results in a report [2]. Before final projects, practical work and its reporting are also an essential part of the undergraduate student experience. In theory, this practical work should enable students to build up their experimental and report writing skills in preparation for the final year. However, despite many study skills books covering scientific writing, it is acknowledged that this is something science students often struggle with [3, 4]. This is illustrated through the variety of approaches taken to address this in the literature, including mini research projects or study skills courses [5, 6]. Although some now question whether the scientific report is a sustainable form of assessment with increasing class sizes [7], most still consider it vital for helping students learn about research and report writing. From reflection on marking student final year reports, it was apparent that many of our students have had insufficient practice at writing complete “scientific paper” style reports by that time, although some do it very well. This is a previously identified problem for undergraduates writing reports, even though there are detailed guidelines, as the format and style expected at university is quite different to that used at school [8]. The more students are embedded in the discipline and reading original literature, the easier it is for them to pick up writing conventions and good ways of presenting data, or even actively deduce conventions from reports [9]. First-year students usually lack sufficient knowledge of biochemical methods to read journal articles well [7], so a different approach is required. The use of exemplars for communicating the style and level of work required is common practice [10], is observed to be favored by students [10, 11], and would seem to be an obvious choice. However, as the subject of practical report are the same every year, teachers are reluctant to share previous student work or provide “model answers” as they do not want to tempt students to plagiarize them. Therefore, a resource was created that modeled a practical report on a topic different to that of the practicals. This approach has also been used to address this problem of scientific report writing in related fields [12]. To clarify the guidelines for writing practical reports, a sample report was designed which incorporated guidelines linked to the text. The report was eight pages with each page consisting of 2/3 “report” and 1/3 notes to illustrate the text. The notes illustrated examples of style and formatting that are used in reports as well as comments on the contents of each section. The notes, the topics for which are summarized in Table I, were similar to the guidelines already provided on how to write reports. The choice of topic was based on the data the author had to hand for an experiment that did not work, to show that good writing does not depend on “correct” results. A pilot evaluation was carried out with small groups of staff and students. Student opinions were sought to find out if they understood the resource and staff opinions were necessary to check that they agreed that this resource embodied good report writing. Opinions from a small group of students in each year were sought using either a short survey, for first and second years, or a focus group for final years. The advantage of running a focus group with the final years was that it also allowed for a discussion of the students experiences of practicals and writing reports. All the responses to the resource were overwhelmingly positive, with the final years being particularly impressed as they could see how it encompassed what they had been learning throughout their degree. The side by side format with the matching of the guidelines to an example was seen as useful. Although final years were united in the opinion that the resource should be useful for all levels, some first and second years thought the topic might be to complex for the beginning of the programme, unless discussed in tutorials. The resource was discussed by the teaching committee as part of the annual review and received several positive comments. It was noted that this would contribute to the new approach we are developing of providing model answers. Due to the diverse nature of tutorials within the department, it was thought that it would be tricky to introduce the resource this way, and an introductory lecture was suggested instead. The resource was made available to all students through the department virtual learning environment. Unfortunately, due to the layout of the environment, it was difficult to find a prominent position for it. To raise awareness of the resource and to help explain it, an introductory lecture to first years was arranged. The lecture included the concept of university practical reports, how to find the resource, a brief introduction to the topic the resource was based on and a review of the sections in the resource, indicating the role of each section in telling the story of the report. To evaluate the uptake and usefulness of the resource, first years were surveyed anonymously during a lecture later in the year. The questionnaire was short, asking if they had used the resource, and if so, what was good and could be improved. If they had not, they were asked why not. The questionnaire was kept simple due to the time constraints of the setting. The idea was to find out if the students had found the resource useful, rather than to evaluate parts of it in detail. A total of 49 out of 78 first years, those who were present in the lecture, completed the questionnaire. Of these, 31 (63%) had used the resource when writing practical reports. Students commented that they found the resource useful for understanding the layout, knowing what to include in each section, formatting figures, and style of writing. Some of the students also commented that having the links between the notes and the example was good, and that this was particularly helpful as it was different to what they had done at school. Of those who had not used it, the main reason (39%) was that they were unaware of it, presumably because they had missed the initial lecture. Other reasons included “could not be bothered” and “could not find it.” Three students (out of 18) commented that they found it hard to use either because it was either on a different topic to their practical or they did not feel it reflected the diversity of marking schemes. Of these, one also admitted to struggling to understand the experiment described. Finally, of the students that used the report, half (15/31) had suggestions for improvement. These fell into three themes: having more samples and examples, having a topic more similar to their practicals, and various suggestions to include things that are currently in the guidelines or should be communicated by the teacher for the practical. Overall, this project seems to be a success, due to the high take up of the resource and the favorable comments. From a student perspective, even if only one of them finds it helpful then it is worthwhile, but there are many comments indicating that a range of students have found it useful. However, the uptake also indicates a communication failure with some students. Running an introductory lecture to the resource would seem to be a reasonable effort to communicate and we cannot accept responsibility for where students have chosen not to engage. However, I hope that as the resource becomes more widely know, not only will students talk about it, and thereby advertise it to their peers, but also that teachers will be able to use it to illustrate their learning outcomes for practical reports. Although teacher opinion was positive, unless it is actively taken up as an example and aligned with marking schemes, this has the potential to be a source of confusion for students. The implementation of all the student suggestions is impractical, although the provision of more examples of figures could be added to the online learning environment. However, it is hoped that this resource will act as a stepping stone for students to go on to read original papers in the topics they are studying. The author thanks the students who provided feedback on the resource and Antje Kuhrs for assisting the focus group. The author also thanks Helen King for advice on the manuscript. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Sample (material)

Report writing

10.1002/bmb.20571

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Citations (9)

The Structure of Testis Angiotensin-Converting Enzyme in Complex with the C Domain-Specific Inhibitor RXPA380^,

Biochemistry (2007)

Hazel Corradi Itai Chitapi B.T. Sewell Dimitris Georgiadis Vincent Dive

Angiotensin I-converting enzyme (ACE) is central to the regulation of the renin−angiotensin system and is a key therapeutic target for combating hypertension and related cardiovascular diseases. Currently available drugs bind both active sites of its two homologous domains, although it is now understood that these domains function differently in vivo. The recently solved crystal structures of both domains (N and C) open the door to new domain-specific inhibitor design, taking advantage of the differences between these two large active sites. Here we present the first crystal structure at a resolution of 2.25 Å of testis ACE (identical to the C domain of somatic ACE) with the highly C-domain-specific phosphinic inhibitor, RXPA380. Testis ACE retains the same conformation as seen in previously determined inhibitor complexes, but the RXPA380 central backbone conformation is more similar to that seen for the inhibitor captopril than enalaprilat. The RXPA380 molecule occupies more subsites of the testis ACE active site than the previously determined inhibitors and possesses bulky moieties that extend into the S2' and S2 subsites. Thus the high affinity of RXPA380 for the testis ACE/somatic ACE C domain is explained by the interaction of these bulky moieties with residues unique to these domains, specifically Phe 391, Val 379, and Val 380, that are not found in the N domain. The characterization of the extended active site and the binding of a potent C-domain-selective inhibitor provide the first structural data for the design of truly domain-specific pharmacophores.

Enalaprilat

10.1021/bi700275e

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Citations (91)

Structure of protoporphyrinogen oxidase from Myxococcus xanthus

Hazel Corradi Anne V. Corrigall Ester Boix C. Gopi Mohan Edward D. Sturrock

Myxococcus xanthus

Protoporphyrinogen oxidase

10.2210/pdb2ive/pdb

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Angiotensin Converting Enzyme N domain glycsoylation mutant (Ndom389) in complex with RXP407

Colin Anthony Hazel Corradi Sylva L. U. Schwager Pierre Redelinghuys Dimitris Georgiadis

10.2210/pdb3nxq/pdb

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Citations (1)