This volume of Modern Aspects of Electrochemistry reviews the latest developments in electrochemical science and technology related to biomedical and pharmaceutical applications. In particular, this book discusses electrochemical applications to medical devices, implants, antimicrobially active materials, and drug delivery systems.

Fibrous Protein: Coiled-Coils, Collagen and Elastomers is the first of a three-part series on Fibrous Proteins. The books are based on a very successful workshop in Alpbach, Austria on the general topic of Fibrous Proteins that gave rise to the award winning issue of Journal of Structural Biology. Part II will contain an extensive discussion of Molecular Motors and Muscle, Part III on Amyloids, Prions and Beta Proteins.
Advances in Protein Chemistry is available online on ScienceDirect full-text online of volumes 53 onwards.
*Reveals new structural and functional aspects of fibrous proteins
*Based on Fibrous Protein workshop in Alpbach, Austria that gave rise to 2003 Nobel Prize winners in Chemistry

This book reflects the use of cyanobacteria for the bioremediation of wastewater through different mechanisms and pathways of transformation and transfer of hazardous substances from one medium to another. The application of microorganisms for bioremediation is determined by their ubiquity, small size, high rate of reproduction and large surface-to-volume cell ratio. Mechanisms of interaction of cyanobacteria with inorganic pollutants include biosorption, bioaccumulation with an opportunity to obtain metal nanoparticles both on the cell surface and inside the cells as well as chelation and inclusion of metals in the composition of certain organic structures. Data presented in the book provides specialists in the field with useful information for bioremediation technologies as well as for obtaining valuable preparations using cyanobacteria.

Michael D. Wendt
Protein-Protein Interactions as Drug Targets

Shaomeng Wang, Yujun Zhao, Denzil Bernard, Angelo Aguilar, Sanjeev Kumar
Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics

Kurt Deshayes, Jeremy Murray, Domagoj Vucic
The Development of Small-Molecule IAP Antagonists for the Treatment of Cancer

John F. Kadow, David R. Langley, Nicholas A. Meanwell, Michael A. Walker, Kap-Sun Yeung, Richard Pracitto
Protein-Protein Interaction Targets to Inhibit HIV-1 Infection
Nicholas A. Meanwell, David R. Langley
Inhibitors of Protein-Protein Interactions in Paramyxovirus Fusion a Focus on Respiratory Syncytial Virus

Andrew B. Mahon, Stephen E. Miller, Stephen T. Joy, Paramjit S. Arora
Rational Design Strategies for Developing Synthetic Inhibitors of Helical Protein Interfaces

Michael D. Wendt
The Discovery of Navitoclax, a Bcl-2 Family Inhibitor

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The volume focuses on the genomics, proteomics, metabolomics, and bioinformatics of a single cell, especially lymphocytes and on understanding the molecular mechanisms of systems immunology. Based on the author's personal experience, it provides revealing insights into the potential applications, significance, workflow, comparison, future perspectives and challenges of single-cell sequencing for identifying and developing disease-specific biomarkers in order to understand the biological function, activation and dysfunction of single cells and lymphocytes and to explore their functional roles and responses to therapies. It also provides detailed information on individual subgroups of lymphocytes, including cell characters, function, surface markers, receptor function, intracellular signals and pathways, production of inflammatory mediators, nuclear receptors and factors, omics, sequencing, disease-specific biomarkers, bioinformatics, networks and dynamic networks, their role in disease and future prospects. Dr. Xiangdong Wang is a Professor of Medicine, Director of Shanghai Institute of Clinical Bioinformatics, Director of Fudan University Center for Clinical Bioinformatics, Director of the Biomedical Research Center of Zhongshan Hospital, Deputy Director of Shanghai Respiratory Research Institute, Shanghai, China.

TheobservationthatabloodclotspontaneouslydissolveswasfirstdescribedbyDenys in1889. Subsequently,thebloodclottingsystemwasshowntobeinvolvedintumor growth. Forexample,asearlyas1925,Fisherreportedthataviantissueexplantstrans- formedtomalignancybyvirusesgeneratedhighlevelsoffibrinolyticactivityundercon- ditionsinwhichculturesofnormalcellsdidnot. In1958,theconceptthatan equilibriumexistedbetweenthetendencyofbloodtoclotandtoremainfluidwaspro- posedbyAstrup. Atthattime,itwasbelievedthatthishemostaticbalancewasexplained bytheabilityofpolymerizingfibrintoorchestrateitsownclearancebystimulatingfib- rinolyticactivity. Sincethesepioneeringstudies,considerableinformationhasaccumu- latedthathasdefinedthecomponentsofthecoagulationandfibrinolyticsystemsand howtheyareinvolvedinphysiologicalandpathophysiologicalprocesses. Plasminogen: Structure, activation, and regulationfocusesonthebasicprinciplesandrecentdevelop- mentsintheplasminogen/plasminresearchfieldandhowtheseresultsprovideacon- ceptualframeworkforanunderstandingofthephysiologicalroleofplasminogenin healthanddisease. Theenzymaticcascadetriggeredbyactivationofplasminogenhasbeenimplicated inavarietyofnormalandpathologicaleventssuchasfibrinolysis,woundhealing,tis- sueremodeling,embryogenesis,angiogenesis,andtheinvasionandmetastasisoftumor cells. Thisimpressivelistofphysiologicalfunctionsforplasminogenreinforcesthewide diversityofrolesthatplasminogenplaysinvariousphysiologicalprocesses. Productive plasmingenerationrequirestheassemblyofbothplasminogenactivatorsandplasmino- genonasolidsupportsuchasthefibrinpolymerorthecellsurface. Theregulationof plasminproductioninvolvesacomplexinterplaybetweentheseplasminogenactivators, plasminogenactivatorinhibitors,andplasmininhibitors. Clearly,theexplosivegrowth inthisresearchfieldandthemanyexcitingdiscoveriessuggeststhattheresearchefforts inthenextdecadewillrevealthemechanismsbywhichthecomponentsoftheplas- minogensysteminteractandregulatebothplasminactivationandfunctionatacellular level. Plasminogen: Structure, activation, and regulationisdividedintotwosections. Thefirstsectiondealswiththestructureandregulationofplasminogen. Thechapters inthissectionrangefromdiscussionsofthestructureofplasminogenandtheregulation oftheplasminogengenetodiscussionsofthestructureandregulationofplasminogen activatorsandplasminogenactivatorinhibitors. Alsoexaminedistherelativelynewdata concerningthegenerationofanti-angiogenicmoleculesfromplasminogen. Thesecond sectiondealswiththephysiologicalandpathophysiologicalrolesofplasminogenaswell astheconsequencesofplasminogengeneknockout. Discussionsinthissectioninclude examinationoftheroleofplasminogeninhematopoieticmalignancies,tumorcell progression,angiogenesis,mammaryglandinvolution,woundhealing,andbone readsorption. xi xii Preface Inclosing,Iwouldliketothankmyadministrativeassistant,Ms. ViSommerfeld,for herinvaluableassistanceandtimelesseffortswiththeorganizationandeditingofthebook. Lastly,Iwouldliketoacknowledgetheeffortsoftheauthorsoftheindividualchapters, whoareauthorities inthisfield,foragreeingtotaketimefrombusyschedulestoprovide thesechaptersinatimelyfashion. DavidMortonWaisman Contents Part I. Plasminogen: Structure and Regulation 1. Human Plasminogen: Structure, Activation, and Function FrancisJ. Castellino and Victoria A. Ploplis 1. Introduction 3 2. StructureofHumanPlasminogen...3 2. 1. PrimaryProteinStructure...3 2. 2. GeneOrganization 5 3. ActivationofHumanPlasminogen...6 3. 1. ActivationbyPhysiologicalActivators 7 3. 1. 1. Urokinase-typePlasminogenActivator...7 3. 1. 2. Tissue-typePlasminogenActivator...8 3. 2. ActivationbyBacterial-derivedPlasminogenActivators...9 3. 2. 1. Streptokinase 9 3. 2. 2. Staphylokinase...9 4. TargetsforPlasminActivity...9 5. DysplasminogenemiasandPhenotypicManifestations 10 6. Conclusions 11 References...11 2. Plasminogen Activators: Structure and Function Vincent Ellis 1. Introduction ...19 2. SerineProteases...20 3. UrokinasePlasminogenActivator,uPA...21 3. 1. SerineProteaseDomain 22 3. 2. N-terminalDomains...24 3. 2. 1. KRModule 24 3. 2. 2. EGModule 24 4. MechanismsRegulatinguPAFunction...25 4. 1. ZymogenActivation...25 4. 2. ZymogenActivity...26 4. 3. ReciprocalZymogenActivation 27 4. 4. uPARStimulationofPlasminogenActivation...27 4. 4. 1. uPAandtheTemplateMechanism 28 4. 4. 2. PlasminogenandtheTemplateMechanism 29 4. 5. AvianuPA,aSpecialCase? 30 xiii xiv Contents 5. TissuePlasminogenActivator,tPA...30 5. 1. SerineProteaseDomain 31 5. 2. N-terminalDomains ,...33 5. 2. 1. KRModules ,. . ,. . ,...33 5. 2. 2. F1-EGSupermodule 33 6.

-Encapsulation by Miniemulsion Polymerization By K. Landfester and C. K. Weiss -Enzyme-Encapsulated Layer-by-Layer Assemblies: Current Status and Challenges Toward Ultimate Nanodevices By K. Ariga, Q. Ji, and J. P. Hill -Non-LBL Assembly and Encapsulation Uses 1 of Nanoparticle-Shelled Hollow Spheres 2 By G.C. Kini, S. L. Biswal, and M. S. Wong -Polymersomes: A Synthetic Biological Approach to Encapsulation and Delivery By M. Massignani, H. Lomas, and G. Battaglia -Reaction Vessels Assembled by the Sequential Adsorption of Polymers By A.D. Price, A.P.R. Johnston, G.K. Such, and F. Caruso

Drug metabolism and transport are very important facets within the discipline of pharmaceutical sciences, with enzyme kinetic concepts utilized regularly in characterizing and modeling the disposition and elimination of drugs. Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications focuses on very practical aspects of applying kinetic principles to drug metabolizing enzymes and transporters. Divided into five convenient sections, topics include the fundamental principles of enzyme kinetics, the kinetics of oxidative and conjugative drug metabolizing enzymes and drug transporters, modeling approaches for both drug metabolizing enzymes and transporters including novel systems biology approaches, understanding of variability both experimental and interindividual (pharmacogenomic), and case studies that provide real life examples of applying these principles. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics especially suitable for the novice, in some cases step-by-step, readily reproducible protocols, and insights to help with troubleshooting and avoiding known pitfalls with extensive cross referencing to assist in learning. Authoritative and easily accessible, Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications serves as a very practical teaching tool for novice, non-mathematically trained scientists interested in these fundamental concepts and as an aid for their supervisors in teaching these principles.

The work reported in this book represents an excellent example of how creative experimentation and technology development, complemented by computational data analysis, can yield important insights that further our understanding of biological entities from a systems perspective. The book describes how the study of a single RNA-binding protein and its interaction sites led to the development of the novel 'protein occupancy profiling' technology that for the first time captured the mRNA sequence space contacted by the ensemble of expressed RNA binders. Application of protein occupancy profiling to eukaryotic cells revealed that extensive sequence stretches in 3' UTRs can be contacted by RBPs and that evolutionary conservation as well as negative selection act on protein-RNA contact sites, suggesting functional importance. Comparative analysis of the RBP-bound sequence space has the potential to unravel putative cis-acting RNA elements without a priori knowledge of the bound regulators. Here, Dr. Munschauer provides a comprehensive introduction to the field of post-transcriptional gene regulation, examines state-of-the-art technologies, and combines the conclusions from several journal articles into a coherent and logical story from the frontiers of systems-biology inspired life science. This thesis, submitted to the Department of Biology, Chemistry and Pharmacy at Freie Universitat Berlin, was selected as outstanding work by the Berlin Institute for Medical Systems Biology at the Max-Delbrueck Center for Molecular Medicine, Germany.

While structure-function relationships of proteins have been studied for a long time, structural studies of RNA face additional challenges. Nevertheless, with the continuous discovery of novel RNA molecules with key cellular functions and of novel pathways and interaction networks, the need for structural information of RNA is still increasing. This volume provides an introduction into techniques to assess structure and folding of RNA. Each chapter explains the theoretical background of one technique, and illustrates possibilities and limitations in selected application examples.

Liposomes are cellular structures made up of lipid molecules. Important as a cellular model in the study of basic biology, liposomes are also used in clinical applications such as drug delivery and virus studies. Liposomes Part E is a continuation of previous MIE Liposome volumes A, B, C and D.
* One of the most highly respected publications in the field of biochemistry since 1955
* Frequently consulted, and praised by researchers and reviewers alike
* Truly an essential publication for anyone in any field of the life sciences

Metal toxicity and deficiency are both common abiotic problems faced by plants. While metal contamination around the world is a critical issue, the bioavailability of some essential metals like zinc (Zn) and selenium (Se) can be seriously low in other locations. The list of metals spread in high concentrations in soil, water and air includes several toxic as well as essential elements, such as arsenic (As), cadmium (Cd), chromium (Cr), aluminum (Al), and selenium (Se). The problems for some metals are geographically confined, while for others, they are widespread. For instance, arsenic is an important toxic metalloid whose contamination in Southeast Asia and other parts of world is well documented. Its threats to human health via food consumption have generated immense interest in understanding plants' responses to arsenic stress. Metals constitute crucial components of key enzymes and proteins in plants. They are important for the proper growth and development of plants. In turn, plants serve as sources of essential elements for humans and animals. Studies of their physiological effects on plants metabolism have led to the identification of crucial genes and proteins controlling metal uptake and transport, as well as the sensing and signaling of metal stresses. Plant-Metal Interactions sheds light on the latest development and research in analytical biology with respect to plant physiology. More importantly, it showcases the positive and negative impacts of metals on crop plants growth and productivity.

Aldehyde Dehydrogenases-The 1992 Perspective.- Metabolic Role of Aldehyde Dehydrogenase.- Effects of Aldehyde Products of Lipid Peroxidation on the Activity of Aldehyde Metabolizing Enzymes in Hepatomas.- Metabolic Interactions of 4-Hydroxynonenal, Acetaldehyde and Glutathione in Isolated Liver Mitochondria.- Biological Role of Human Cytosolic Aldehyde Dehydrogenase 1: Hormonal Response, Retinal Oxidation and Implication in Testicular Feminization.- Human Cytosolic Aldehyde Dehydrogenase in Androgen Insensitivity Syndrome.- The Use of Immortalized Mouse L1210/OAP Cells Established in Culture to Study the Major Class 1 Aldehyde Dehydrogenase-Catalyzed Oxidation of Aldehydes in Intact Cells.- Enhanced Transcription of the Cytosolic ALDH Gene in Cyclophosphamide Resistant Human Carcinoma Cells.- Attempts to Increase the Expression of Rat Liver Mitochondrial Aldehyde Dehydrogenase in E. coli by Altering the mRNA.- Preliminary Characterization of the Rat Class 3 Aldehyde Dehydrogenase Gene.- Human High-Km Aldehyde Dehydrogenase (ALDH3): Molecular, Kinetic, and Structural Features.- Overexpression or Polycyclic Aromatic Hydrocarbon-Mediated Induction of an Apparently Novel Class 3 Aldehyde Dehydrogenase in Human Breast Adenocarcinoma Cells and Its Relationship to Oxazaphosphorine-Specific Acquired Resistance.- Tumor-Associated Aldehyde Dehydrogenase (ALDH3): Expression in Different Human Tumor Cell Lines with and without Treatment with 3-Methylcholanthrene.- Sexual Differentiation in the Induction of the Class 3 Aldehyde Dehydrogenase.- Mouse Class 3 Aldehyde Dehydrogenases: Positive and Negative Regulation of Gene Expression.- Human Stomach Aldehyde Dehydrogenase, ALDH3.- Bovine Corneal Aldehyde Dehydrogenases: Evidence for Multiple Gene Products (ALDH3 and ALDHX).- Carbonyl-Metabolizing Enzymes and Their Relatives Recruited as Structural Proteins in the Eye Lens.- Members of the ALDH Gene Family are Lens and Corneal Crystalline.- Retinoic Acid Synthesis in the Developing Retina.- Human Liver High Km Aldehyde Dehydrogenase (ALDH4): Properties and Structural Relationship to the Yeast Glutamic ?-Semialdhyde Dehydrogenase.- Effect of Some Compounds Related to Disulfiram on Mitochondrial Aldehyde Dehydrogenase in Vitro and in Vivo.- Photoaffinity Labeling of Aldehyde Dehydrogenase from Horse Liver by P1-N6-(4-Azidophenylethyl) Adenosine-P2[4-(3-Azidopyridinio)Butyl] Diphosphate.- Aldehyde Dehydrogenase: Aldehyde Dehydrogenation and Ester Hydrolysis.- Is the Single Site Binding Model for Aldehyde Dehydrogenase an Oversimplification? The One-Site, Two-Site Debate Revisited.- Crystallization and Preliminary X-Ray Analysis of Bovine Mitochondrial Aldehyde Dehydrogenase and Human Glutathione-Dependent Formaldehyde Dehydrogenase.- Aldo-Keto Reductases: An Overview.- Location of an Essential Arginne Residue in the Primary Structure of Pig Aldose Reductase.- Cys298 Is Responsible for Reversible Thiol-Induced Variation in Aldose Reductase Activity.- Substrate Specificity of Reduced and Oxidized Forms of Human Aldose Reductase.- Kinetic Alteration of Human Aldose Reductase by Mutagenesis of Cysteine Residues.- Inhibition of Aldose Reductase by (2, 6-Dimethylphenylsulphonyl) Nitromethane: Possible Implications for the Nature of an Inhibitor Binding Site and a Cause of Biphasic Kinetics.- Sepiapterin Reductase and ALR2 ("Aldose Reductase") from Bovine Brain.- Polymorphisms of the Aldose Reductase Locus (ALR2) and Suseptibility to Diabetic Microvascular Complications.- Polycyclic Aromatic Hydrocarbons and Phenolic Antioxidants do not Significantly Induce Carbonyl Reductase in Human Cell Lines.- The Purification and Properties of a Novel Carbonyl Reducing Enzyme from Mouse Liver Microsomes.- Properties and Stereoselectivity of Carbonyl Reductases Involved in the Ketone Reduction of Warfarin and Analogues.- Activation of Pulmonary Carbonyl Reductase by Aromatic Amines and Pyridine Ring-Containing Compounds.- Unique Dihydrodiol Specific Dehydrogena...

The first contribution presents coumarins, the largest group of 1-benzopyran derivatives found in plants. Coumarin chemistry remains one of the major interest areas of phytochemists, especially because of their structural diversity and medicinal properties, along with the wide-ranging bioactivities of these compounds, inclusive of analgesic, anticoagulant anti-HIV, anti-inflammatory, antimicrobial, antineoplastic, antioxidant, and immunomodulatory effects. The second contribution presents a comprehensive survey of the many aspects of PAD biochemistry and physiology. The third contribution gives a comprehensive overview of secondary metabolites from higher fungi, with more than 700 references highlighting the isolation, structure elucidation, biological activities, chemical synthesis, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms.

This thesis outlines the first synthesis of a new complex branched polymer architecture that aims to combine the benefits of dendrimers with the simplicity of conventional polymerisation. There is no other available literature on these remarkable materials, dubbed hyperbranched polydendrons, due to their novelty. The new materials were shown to have very high molecular weights (>1,000,000 g/mol), exceptional self-assembly and encapsulation behaviour and unparalleled functionalisation capabilities, and were studied pharmacologically to determine their potential as oral nanomedicine candidates. The detailed investigation of the chemical variables involved in synthesising hyperbranched polydendrons has shown that their self-assembly and pharmacological behaviour can be turned on and off and fine-tuned by altering the composition of the materials. The permeation of the self-assembled particles through model gut epithelium suggests the potential for oral dosing of drug loaded nanomedicines that result in circulating nanoparticles - a research goal that is currently being pursued by several groups around the globe.

"Immuno Systems Biology" aims to study the immune system in the more integrated manner on how cells and molecules participate at different system levels to the immune function. Through this bookKumar Selvarajoointroduces to physicists, chemists, computer scientists, biologists and immunologists the idea of an integrated approach to the understanding of mammalian immune system. Geared towards a researcher with limited immunological and computational analytical experience, the book provides a broad overview to the subject and some instruction in basic computational, theoretical and experimental approaches. The book links complex immunological processes with computational analysis and emphasizes the importance of immunology to themammalian system. "

This book discusses the latest research and new techniques in the field of lactic acid bacteria, including comparative genomics, transcriptomics, proteomics and metabolomics. It also introduces the omics and functional evaluation in detail and shows the links between lactic acid bacteria and gut health and host immunity. Summarizing the biotechnological advances in lactic acid bacteria for food and health, it is a valuable resource for researchers and graduate students in the fields of food microbiology, bioengineering, food science, nutrition and health.

This fourth volume in the series on biochemistry looks at foundations in modern biochemistry. Topics covered include: the genetic solution; the genetic basis of development; DNA repair; evolution in an RNA world; nitrogen fixation; solute channels; viruses; biochemistry in retrospect and propspect.

This updated monograph deals with methanogenic endosymbionts of anaerobic protists, in particular ciliates and termite flagellates, and with methanogens in the gastrointestinal tracts of vertebrates and arthropods. Further chapters discuss the genomic consequences of living together in symbiotic associations, the role of methanogens in syntrophic degradation, and the function and evolution of hydrogenosomes, hydrogen-producing organelles of certain anaerobic protists. Methanogens are prokaryotic microorganisms that produce methane as an end-product of a complex biochemical pathway. They are strictly anaerobic archaea and occupy a wide variety of anoxic environments. Methanogens also thrive in the cytoplasm of anaerobic unicellular eukaryotes and in the gastrointestinal tracts of animals and humans. The symbiotic methanogens in the gastrointestinal tracts of ruminants and other "methanogenic" mammals contribute significantly to the global methane budget; especially the rumen hosts an impressive diversity of methanogens. This makes this updated volume an interesting read for scientists and students in Microbiology and Physiology.

Nuclear G-Protein Coupled Receptors: Methods and Protocols is a compilation of a number of conceptual and methodological aspects important for the validation and characterization of intacrine signaling systems. To date, the best-characterized intracrine signaling system is that of angiotensin II (Ang II), covered in depth in various chapters. Methodology to study the subcellular localization and function of GPCRs and other signaling systems is provided, as well as numerous chapters focusing on methods designed to understand signaling mediated by nuclear and other internal GPCRs. Methods are also described to study the formation of second messengers such as cAMP and to study the trafficking of receptors from the cell surface. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Nuclear G-Protein Coupled Receptors: Methods and Protocols seeks to serve both professionals and novices with state-of-the-art approaches to characterize what is becoming a common theme in cellular signaling.

This book offers an overview of our current understanding of host defense peptides and their potential for clinical applications as well as some of the obstacles to this. The chapters, written by leading experts in the field, detail the number and diversity of host defense peptides, and discuss the therapeutic potential not only of antibacterial, but also of antifungal, antiviral, plant antimicrobial and anticancer host defense peptides. The authors provide new insights into their mechanisms of action and their immunomodulatory properties, and review recent advances in the design of novel therapeutic molecules. Lastly, their potential to prevent preterm births and Staphylococcus aureus infections is highlighted. The book is of interest to researchers, industry and clinicians alike.

This book focuses on the application of fluorescence to study motor proteins (myosins, kinesins, DNA helicases and RNA polymerases). It is intended for a large community of biochemists, biophysicists and cell biologists who study a diverse collection of motor proteins. It can be used by researchers to gain an insight into their first experiments, or by experienced researchers who are looking to expand their research to new areas. Each chapter provides valuable advice for executing the experiments, along with detailed background knowledge in order to develop own experiments.

In this volume expert researchers in the field detail the operations of microchip capillary electrophoresis. Chapters focus on small molecule, biomolecule applications, various detection modes, and sample preparation approaches are described. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Microchip Capillary Electrophoresis Protocol aids scientists in continuing to study microchip capillary electrophoresis.

As part of a collaboration between two different groups in chemistry and biochemistry, Thom Sharp presents here his thesis work on the development of new methods for cryoelectron microscopy. Throughout his Ph.D., Thom had to master a whole range of techniques including modelling, molecular biology and microscopy. Using these skills to tackle an outstanding problem, the pursuit of high-resolution structures of peptide-based materials, Thom highlights in this thesis his newly developed methods for analysing and processing this particular type of electron microscopy data. This thesis gives the first molecular description of a de-novo designed peptide-based material. In general, this research will have a huge impact on the peptide assembly field, and also in electron microscopy as it introduces new methods and approaches, all of which are Thom's inventions and are described in this thesis.