1. HIV/AIDS. A central topic of our studies has been reverse transcriptase (RT), an essential component of the AIDS virus and the target of many of the most widely used anti-AIDS drugs. Using the techniques of X-ray crystallography, our team has solved the three-dimensional structures of HIV-1 RT in complex with antiviral drugs and segments of the HIV genome. These studies have illuminated the working of an intricate and fascinating biological machine in atom-by-atom detail and have yielded numerous novel insights into polymerase structure-function relationships, detailed mechanisms of drug resistance, and structure-based design of RT inhibitors. Our crystal structures enabled the discovery and development of two drugs (etravirine/TMC125 and rilpivirine/TMC278), currently being used for treating HIV infection, that have exceptional potency against drug-resistant variants. We are continuing to study the molecular basis of HIV RT function, inhibition, and resistance, and are pursuing additional avenues for molecular targeting of HIV RT, including development of RNase H inhibitors as potential drugs. Recent success in protein and crystal engineering yielding high-resolution crystals of HIV-1 RT (diffracting in some cases to 1.5 Å resolution) has enabled a systematic application of crystallographic drug-like fragment screening, revealing several novel allosteric sites for inhibiting RT polymerase and RNase H activity. Recent work applying crystallographic fragment screening to HIV-1 integrase has revealed novel chemical scaffolds for allosteric inhibition of HIV-1 IN (ALLINIs).

2. Bacterial disease targets including tuberculosis and MRSA. With the laboratory of Richard Ebright we are studying structures of bacterial RNA polymerase—the central transcription machinery and a validated target for treatment of tuberculosis. Among the key structures analyzed are T. thermophilus RNA polymerase complexes with antibiotics streptolydigin and myxopyronin, and an open-promoter complex that has revealed the structural basis of transcription initiation.

3. Influenza virus. My laboratory has also focused on developing a better understanding of the molecular basis of influenza virus pathogenesis, and applying our expertise in structural biology and drug design to developing novel flu drugs targeting the viral polymerase. Several years ago we initiated crystallographic fragment screening against the cap-snatching endonuclease of 2009 H1N1 pandemic influenza A virus. We succeeded in identifying drug-like fragments that bound to the endonuclease active site, chelated the catalytic metal ions, and inhibited enzymatic activity. Working with medicinal chemist Edmond LaVoie we undertook a structure-based optimization effort to evolve a fragment with initial IC 50 of 16 micromolar to a lead compound that inhibits the enzyme at 11 nanomolar concentration, and the lead compound was shown to have anti-influenza activity by collaborator Luis Martinez-Sobrido at the University of Rochester Medical Center. We are continuing to use this structure-based drug design platform to create derivatives of the most potent 3-hydroxypyridinone lead that will have improved activity in thwarting influenza virus infection.

Eddy Arnold is Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and a Resident Faculty Member at the Center for Advanced Biotechnology and Medicine. He has authored more the 240 scientific publications. Among his awards and honors are two NIH MERIT Awards (1998-2008, 2009-2019) and the Hyacinth Award “Honoring Advances in the Struggle Against AIDS” (2013). He is an elected Fellow of the American Association for the Advancement of Science (2001) and in the American Academy of Microbiology (2006).

In parallel to her research, Berman is extremely active in the community, and serves a variety of advisory committees, professional societies, and editorial boards. Berman is a Fellow of the American Association for the Advancement of Science, the Biophysical Society, and the American Crystallographic Association (ACA). She is a recipient of the American Society for Biochemistry and Molecular Biology's DeLano Award (2013), Protein Society's Carl Brändén Award (2012), and the ACA's Buerger Award (2006).

3. Industry: companies founded, boards etc Astex Therapeutics: Co-founder, 1999, Board Member, Chair SAB 1999-2011; Biofabrika: Co-founder, 1989-1991; Celltech: Non-executive Director, 1996-2004; Chair SAB, 1998- 2004; UCB Celltech, Science Advisory Board, 2005; SmithKline Beecham: International R&D Board, 1997-1999; Pfizer: Consultant in UK and USA, 1983-1990; Parke Davis: US Consultant, 1987-1990; Abingworth Management Ltd, Science Advisory Board, 1986-1990, 1996-; Syntaxin: member of SAB; FEI: SAB 2007-2010; Isogenica, Scientific Consultant, 2008 -

4. Public Bodies: Research Councils: AFRC Council (1985-1990); DG, (1991-1994); BBSRC Founding CEO, BBSRC, 1994-1996. Non-executive Chairman of BBSRC: 2009 - Royal Commission on Environmental Pollution, Chairman (1998-2005); Advisory Council on Science and Technology (ACOST) Cabinet Office (1988-1990).

With a broad interest in both chemistry and physics I studied for a BA in Natural Sciences at the University of Cambridge. Continuing within the chemistry department at Cambridge I completed a PhD in NMR techniques development. This allowed me to combine aspects of quantum mechanics, numerical methods and computer programming to develop new methods that I was then faced with the challenge of implementing in practice within organic and biological systems.

I joined Glaxo (GSK) in 1993 as a temporary postdoctoral researcher and have never left.

I currently lead a small group that spans X-ray crystallography, NMR and biophysics at GSK's UK research site in Stevenage, which matches my personal expertise. The group supports crystallography and biophysical studies from mode-of-action analysis to fragment screening across a wide range of therapeutic areas.

My current personal research focus is epigenetics (epi-readers and epi-enzymes), where I carry out the crystallography for many of these targets and co-lead a drug discovery program focused on bromodomains.

Dr. Stephen Cusack obtained his first degree in physics and theoretical physics at Cambridge University and subsequently a PhD in theoretical solid-state physics at Imperial College, London. He then switched his interests to molecular biology and in 1977 joined the European Molecular Biology Laboratory in Grenoble, France, where he has been ever since, first as a post-doc, then a staff scientist and, since 1989, as Head of Outstation and group leader in the structural biology of protein-RNA and viral proteins. The EMBL Grenoble Outstation collaborates closely with the European Synchrotron Radiation Facility in Grenoble to provide state-of-the-art beamline facilities for structural biology. The Outstation is also a founder member of the Partnership for Structural Biology (http://www.psb-grenoble.eu/) which provides an integrated environment for multidisciplinary structural biology. Dr. Cusack is also director of the EMBL-CNRS-Grenoble University International Unit for Virus Host Cell Interactions and extensively involved in European level structural biology initiatives such as Instruct (http://www.structuralbiology.eu/).

His research group uses X-ray crystallography as a central technique to study the structure-function relationships of complexes involving RNA in eukaryotic cells, for instance RNA maturation (5' cap-dependent processes), mRNA quality control (nonsense-mediated decay) and translational fidelity (aminoacylation and editing mechanisms of aminoacyl-tRNA synthetases). In parallel Dr. Cusack has focussed on the structural biology of viral proteins, most notably adenovirus capsid proteins and negative strand RNA virus polymerases, notably that of influenza and La Crosse viruses. Both the aminoacyl-tRNA synthetase and influenza polymerase projects are leading to development of novel antibiotics and anti-virals in collaboration with pharmaceutical companies.

Colin has a background in industry, with 7 years at Pfizer in the UK, where he established the protein crystallography group and a year in an informatics role at Pfizer Cambridge US. Following this he spent 7 years at Celltech/UCB leading the computer assisted drug design team and the investigational chemistry group, who were tasked with developing small molecule approaches to established antibody targets.

Colin's scientific interests range from structural biology though to bioinformatics (he co-authored the paper ‘The Druggable Genome'), medicinal chemistry (with colleagues he introduced the concept of ‘ligand efficiency'), structural chemistry and chemoinformatics.

Selected Publications:

Leach, A.R and Hann, M.M.. Molecular complexity and fragment-based drug discovery: ten years on. Current Opinion in Chemical Biology 2011, 15:489–496

Hann, M. M. Molecular obesity, potency and other addictions in drug discovery. MedChemComm (2011), 2(5), 349-355.

Hann, M. M.; Leach, A. R.; Burrows, J. N.; Griffen, E. Lead discovery and the concepts of complexity and lead-likeness in the evolution of drug candidates. Comprehensive Medicinal Chemistry II (2006), 4 435-458. .

Leach, AR.; Hann, MM.; Burrows, JN.; Griffen, EJ. Fragment screening: an introduction. . Molecular BioSystems (2006), 2(9), 429-446. Publisher: Royal Society of Chemistry,

Hann, MM.; Oprea, TI. Pursuing the leadlikeness concept in pharmaceutical research. Current Opinion in Chemical Biology (2004), 8(3), 255-263

Hann, MM.; Leach, AR.; Harper, G. Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery. Journal of Chemical Information and Computer Sciences (2001), 41(3), 856-864.

Leach, A. R.; Hann, M. M.. The in silico world of virtual libraries. Drug Discovery Today (2000), 5(8), 326-336.

Bravi, G., Green, D. V. S.; Hann, M. M.; Leach, A.R . PLUMS: a Program for the Rapid Optimization of Focused Libraries. JCICS (2000), 40(6), 1441-1448.

Leach, AR.; Green, DVS Hann, MM.; Judd, DB.; Good, AC. Where are the GaPs? a rational approach to monomer acquisition and selection. Journal of Chemical Information and Computer Sciences (2000), 40(5), 1262-1269.

Hann, MM; Green, R. Chemoinformatics - a new name for an old problem? Current Opinion in Chemical Biology (1999), 3(4), 379-383. .

Hann MMS; Hudson B; Lewell X; Lifely R; Miller L; Ramsden N Strategic pooling of compounds for high-throughput screening . Journal of chemical information and computer sciences (1999 Sep-Oct), 39(5), 897-902.

Lewell X Q; Judd D B; Watson S P; Hann M M RECAP--retrosynthetic combinatorial analysis procedure: a powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry. Journal of chemical information and computer sciences (1998 May-Jun), 38(3), 511-22.

I have mentored 6 Ph. D. students and 8 postdoctoral fellows, published 89 papers in peer-reviewed journals and three books, organized 7 international meetings and gave 88 conferences at international meetings. I participated in six drug design projects in collaboration with industrial companies, where I had the task of solving the protein-inhibitor complexes.

In 1997 I joined Merck and Co., Inc, where I was involved in several projects, providing structural biology support for diabetes, inflammation and oncology targets. I developed and still maintain a particular interest in the structural aspects of Protein Kinases inhibition. My more recent work focused on the diabetes target DPP-4, and on how structural biology and modeling have helped the development of several potent inhibitors. In November 2008 I joined Schering-Plough (now part of Merck), where I have continued my work as protein crystallographer.

I published over 60 papers in peer-reviewed journals, and I have been invited to give several talks about my research at local universities and national and international meetings.

Software tools
BUSTER Maximum Likelihood X-ray refinement http://www.globalphasing.com/buster/wiki/
Grade ligand restraint dictionaries from CSD and QM information
Grade Web Server http://grade.globalphasing.org
rhofit: flexible ligand fitter that copes with macrocycles
buster-report: refinement analysis with emphasis on ligands http://www.globalphasing.com/buster/wiki/index.cgi?BusterReport

Ph.D. Biophysics Imperial College London, 1987-1991, Working with Prof. David Blow on simulation of enzyme reaction mechanism.
Post doc. and Wellcome Trust Career Development Fellowship Dept of Crystallography, Birkbeck College, 1992-1997. Working with Profs Julia Goodfellow and Bonnie Wallace on simulation and analysis of gramicidin.
Lecturer University of Birmingham 1997-2003. Working on protein modelling, MD simulation and design of chemically-modified proteins. 4 successful PhD supervised. Many publications.
Scientist programmer Global Phasing Ltd 2003 to date. Finally saw the light and started to work on protein structure with data!

Stroud focuses on understanding function at the atomic level, and at the levels of macromolecular organization. He has a major commitment to understanding the structure and function of classes of integral membrane proteins. In enzymology he focused on the structural basis for mechanisms, and on discovery of new principles for drug discsovery aimed at enzymes and proteins. These include trypsin and serine proteases, thymidylate synthase, HIV protease, and HIV integrase. He currently studies specificity and mechanism of enzymes that modify RNA, particularly pseudo-uridine synthases, and RNA methylases. He also works with Peter Walter on the process of recognition of unfolded proteins inside the endoplasmic reticulum via the unfolded protein response, and the method of targeting membrane proteins to and through the translocating pore in the membrane.

His focus in the lecture is on facilitating understanding how transmembrane proteins function at the level of the atomic basis for their selectivity and mechanisms. In this area he first determined the profile structures of the neurochemical acetylcholine receptor in the 1970s. He discovered the first atomic structure of an integral membrane protein in the aquaporin class in 2000, followed by several more structures and functional assays of conductivity to delineate mechanisms. His group determined the mechanism of the first ammonia transporter, and a human Rh factor. This was followed with his determination of the mechanisms of regulation of bacterial ammonia channels by the soluble sensory protein GlnK. He has originated new methods in the expression and purification of fully functional heterologously expressed

Stroud is the 2009 winner of the Hans Neurath award of the Protein Society, and the 2009 winner of the Anatrace award of the Biohysical society. He is a member of the National Academy of Sciences, fellow of the American Academy of Arts and Sciences and a Fellow of the Royal Society of Medicine (United Kingdom) (http://msg.ucsf.edu/stroud/index.html).

Wells is a professor and chair of the Department of Pharmaceutical Chemistry in the UCSF School of Pharmacy. He holds a combined appointment as professor in the Department of Cellular & Molecular Pharmacology in the School of Medicine. He joined UCSF in 2005 as holder of the Harry Wm. and Diana V. Hind Distinguished Professorship in Pharmaceutical Sciences. Wells also founded and directs the Small Molecule Discovery Center (SMDC) located at UCSF's Mission Bay campus. He earned a PhD degree in biochemistry from Washington State University with Professor Ralph Yount in 1979 and completed postdoctoral work at Stanford University School of Medicine with Professor George Stark in 1982. Before joining UCSF, Wells was a founding scientist in Genentech's Protein Engineering Department and in 1998 co-founded Sunesis Pharmaceuticals.

Wells is a recipient of the Hans Neurath Award by the Protein Society, the Pfizer Award and Smissman Award given by the American Chemical Society, the Perlman Lecture Award given by the ACS Biotechnology Division, the du Vigneaud Award given by the American Peptide Society, the Merck Award from the ASBMB and in 1999 a member of the National Academy of Sciences.