SCIENCE & TECHNOLOGY
FERTILIZATION FORMULA
NEWSCO M
negated the role of ZP3 sugars in sperm-egg recognition, says Pablo E. Visconti, who studies fertilization at the University of Massachusetts, Amherst. Then this past July, Jurrien Dean, a developmental biologist at the National Institute of Diabetes & Digestive & Kidney Diseases, Researchers step closer to the MOLECULAR MECHANISM and his colleagues published a paper in Scibehind the sperm and egg union ence that struck a major blow to the textbook SARAH EVERTS, C&EN BERLIN ZP3-sugar model (2010, 329, 216). They engineered mice that are normal except for mutations of the serine residues IT’S PRETTY MUCH the most important are dressed in a thick protective coat of proin ZP3, the ones that supposedly anchored encounter of your life, but scientists still teins and sugars called the zona pellucida. the sugar that sperm recognize. In the endon’t know precisely how your father’s In mammals, the three proteins that make gineered mice, one or both of the serines sperm bound to your mother’s egg, injected up the ZP are typically called ZP1, ZP2, and were replaced with alanine residues, which its genetic package, and then prevented ZP3, and it’s these sugar-decorated proteins cannot anchor sugars. If the textbook modany other aspiring contenders from doing that a sperm must recognize to successfully el had been correct, these engineered mice the same. fertilize an egg. would have been infertile because their ZP3 Even though this year’s Nobel Prize in proteins could not anchor the sugar that Physiology or Medicine went to Robert IF YOU CRACK open a developmental biolsperm use to bind and fertilize an egg. InEdwards for developing in vitro fertilizaogy textbook, you’ll likely encounter the stead, the mice bred normally. The normal tion—whereby sperm and egg fusion ocfertilization model that was first proposed fertility of these mutant mice “is not concurs on a lab bench—nature’s precise bioin the 1980s by Paul M. Wassarman at the sistent” with models that require serinechemical mechanism for this matchmaking Mount Sinai School of Medicine in New attached sugars to “play an essential role in process is a source of thorny debate among York City, which has been tweaked only sperm-egg recognition,” the authors note. developmental scientists. In the past few slightly in the 30 years since. In this model, Instead, the work of Dean and his colmonths, however, two papers have begun proteins on the sperm head interact leagues adds weight to a to clarify some of the important steps at with essential sugars attached to competing fertilization MAKING A MOVE the foundation of life. One paper reports two specific serine residues on ZP3. mechanism. This theory Sperm attempt the crystal structure of an egg protein inAlthough this theory was pervasive, to fertilize an egg, proposes that a sperm recogvolved in fertilization, and the second, usuntil this past summer, no experinizes the overall macromowhich is about ing animal models and genetics, questions ments had conclusively supported or 100 µm wide. lecular structure of the egg’s a long-standing theory about protective coating. After this sperm-egg fusion. recognition, the egg’s ZP2 The lure of finally resolvproteins are chopped up, ing the molecular mechacausing the sugary protein nisms of fertilization is partly coating to be remodeled about the prospect of develsuch that other enthusiastic oping cures for infertility or sperm cannot weasel their new forms of contraception. way into the now-fertilized “But it’s more primal than egg. that,” says Luca Jovine, an After Dean’s Science paper X-ray crystallographer at appeared, Visconti and anthe Karolinska Institute in other cell biologist, Harvey Stockholm. It’s about getting Florman at the University insight on the propagation of Massachusetts Medical and survival of our species, School in Worcester, wrote “something we all relate to,” a commentary that tried he says. to strike a peaceful middle Although humans still ground between the two comstruggle with the technicalipeting theories (Sci. Signaling ties, evolution worked out 2010, 3, pe35). “Dean’s paper the kinks of fertilization proved that the two serines hundreds of millions of years on ZP3 aren’t involved in ferago. Since then, animals as tilization,” but it didn’t rule diverse as mollusks, reptiles, out that a sugar attached to a and humans have multiplied different amino acid could be using eggs and sperm. Most acting as a binding partner, animals possess eggs that Visconti says. WWW.CEN-ONLINE.ORG
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ACS Center for Professional Development
2011 Planning Guide Short Courses
Webcast Courses
Leadership Development System
ACS-Harvard Courses
American Chemical Society
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The ACS Center for Professional Development
is the place to go for technical, leadership, business, and soft skills training. ACS offers a variety of programs to help you develop your professional skills including Short Courses, Webcast Short Courses, ACS Leadership Courses, and ACS-Harvard online courses.
Short Courses and Webcast Short Courses The ACS Department of Professional Education offers short courses and webcast short courses designed to help chemical scientists and technicians keep current in today’s competitive marketplace. We believe that finding the training you need shouldn’t be hard. That’s why we dramatically revamped our website and registration system; now you can find the courses you’re looking for with ease.
Check out all of our offerings at www.ProEd.acs.org/2011 You can now search our short courses and webcast courses by topic area, date, or location; you can even browse our full instructor list. We are continuously investing in new course development, so if you don’t see what you’re looking for, just drop us a line at
[email protected], and we’ll do our best to serve your technical training needs.
ACS Leadership Development System The ACS Leadership Development System is a comprehensive leadership curriculum that provides you with practical courses to advance your career, help you to be more effective in your position, and equip you with tools to more effectively lead ACS volunteer initiatives. The suite of courses provides you with an opportunity to take courses in a face-to-face setting as well as online (24/7).
Go to www.acs.org/leaderdevelopment
ACS-Harvard Online Courses Scientists with both technical and business skills are highly valued by employers. By taking ACS-Harvard online courses, you’ll become more competitive in the job market.
Go to www.acs.org/harvard
American Chemical Society
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2011 Short Courses
Calendar ACS will be offering Short Courses in these locations, tentatively scheduled for the following months. February Woodbridge, NJ | February 22 - 25 w Chemical Engineering and Process Fundamentals for Chemists w Effective Supervision of Scientists and the Technical Staff w Essentials of Medicinal Chemistry and Pharmacology w Experimental Design for Productivity and Quality in Research & Development w Introduction to Modern Mass Spectrometry w Laboratory Safety & Health w Pharmacokinetics and Pharmacodynamics: Principles and Applications in Pre-Clinical Drug Development w Process Research in the Pharmaceutical Industry: The Design and Development of Practical Syntheses w Recent Developments in Organic Synthesis
March Atlanta, GA (Pittcon) | March 12 - 13 w Ecological Impact of Chemicals w Effective Supervision of Scientists and the Technical Staff w Human Health & Toxic Impact of Chemicals w Introduction and Use of Standard Methods for Environmental Regulatory Analysis and Compliance w Introduction to Process Analytical Technology
Anaheim, CA | March 26 - 30 (ACS Spring National Meeting) w Capillary Electrophoresis of Biomolecules w Chemical Engineering and Process Fundamentals for Chemists w Dispersions in Liquids: Suspensions, Emulsions, and Foams w Drug-like Properties: Optimizing Pharmacokinetics and Safety in Drug Discovery w Effective Auditing/Inspection Process for Pharmaceutical Laboratories w Fundamentals of High Performance Liquid Chromatography w Fundamentals of Model Building w Groundwater Geochemistry for Chemists w Introduction to Modern Mass Spectrometry w Introduction to Safe Handling of Nanomaterials in the Workplace w Mastering the Art of Writing Reasonable Organic Reaction Mechanisms w Methods Development, Validation Procedures, and Regulatory Compliance Issues w NMR Spectral Interpretation and Organic Spectroscopy: A Problem-Based Learning Approach w Organic Synthesis: Methods and Strategies for the 21st Century Chemist
w Polymer Chemistry w Polymeric Coatings w Practical Approaches to Patents and Other Forms of Intellectual Property w Practical HPLC in Pharmaceutical Analysis w Project Management for Technical Professionals w Statistical Analysis of Laboratory Data w Structure Based Drug Design
april St. Louis, MO | April 11 - 13 w Chemical Engineering for Chemists w Experimental Design for Productivity and Quality in Research & Development w Fundamentals of Food Packaging w Laboratory Safety w Practical Applications of Mass Spectrometry for Small Molecules
april/May Philadelphia, PA | April 30 - May 3 w Analysis and Interpretation of Mass Spectral Data w Analytical Method Transfer of Pharmaceutical Products w Chemical Engineering and Process Fundamentals for Chemists w Drug-like Properties: Optimizing Pharmacokinetics and Safety in Drug Discovery w Essentials of Medicinal Chemistry and Pharmacology w Effective Auditing/Inspection Process for Pharmaceutical Laboratories w Organic Synthesis: Methods and Strategies for the 21st Century Chemist w Pharmacokinetics and Pharmacodynamics: Principles and Applications in Pre-Clinical Drug Development w Statistical Analysis of Laboratory Data
Early registration and group discounts are available. Visit www.ProEd.acs.org/2011 for more details. Certain restrictions may apply.
Questions? www.ProEd.acs.org/2011
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2011 Short Courses Calendar continued August Denver, CO | August 26 - 31 (ACS Fall National Meeting) w Chemical Engineering and Process Fundamentals for Chemists w Chemical Toxicology: A Chemist’s Roadmap to Reduce Bioactivation Liabilities in Drug Candidates w Drug-like Properties: Optimizing Pharmacokinetics and Safety in Drug Discovery w Effective Supervision of Scientists and the Technical Staff w Effective Technical Writing w Experimental Design for Productivity and Quality in Research & Development w Food Science w Infrared Spectral Interpretation: A Systematic Approach w Introduction and Use of Standard Methods for Environmental Regulatory Analysis and Compliance w Introduction to Drug Metabolism: Role and Practice in Drug Discovery and Development w Introduction to Modern Mass Spectrometry w Mastering the Art of Writing Reasonable Organic Reaction Mechanisms w NMR Spectral Interpretation and Organic Spectroscopy: A Problem-Based Learning Approach w Practical and Applied Gas Chromatography w Project Management for Technical Professionals w Solid-State Organic Chemistry w Statistical Analysis of Laboratory Data w Structure Determination of Small Molecule Organic Compounds Using One and Two dimensional NMR Spectroscopy
september Boston, MA | September 19 - 22 w Analytical Method Transfer of Pharmaceutical Products w Capillary Electrophoresis of Biomolecules w Computer Assisted Drug Design w Critical cGMP and ICH regulations for Pharmaceutical Laboratories w Effective Supervision of Scientists and the Technical Staff w Essentials of Medicinal Chemistry and Pharmacology w Fundamentals of High Performance Liquid Chromatography w Fundamentals of Model Building w Laboratory Safety & Health w Organic Synthesis: Methods and Strategies for the 21st Century Chemist w Pharmacokinetics and Pharmacodynamics: Principles and Applications in Pre-Clinical Drug Development w Practical and Applied Gas Chromatography
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w Practical Applications of Mass Spectrometry for Small Molecules w Practical Approaches to Patents and Other Forms of Intellectual Property w Process Research in the Pharmaceutical Industry: The Design and Development of Practical Syntheses
october Chicago, IL | October 11 - 15 w Analysis and Interpretation of Mass Spectral Data w Dispersions in Liquids: Suspensions, Emulsions, and Foams w Drug-like Properties: Optimizing Pharmacokinetics and Safety in Drug Discovery w Effective Supervision of Scientists and the Technical Staff w From Kitchen to Plant: Industrial Production of Processed Food Products w Laboratory Safety w Methods Development, Validation Procedures, and Regulatory Compliance Issues w Organic Synthesis: Methods and Strategies for the 21st Century Chemist w Polymeric Coatings
november La Jolla, CA | November 7 - 10 w Analysis and Interpretation of Mass Spectral Data w Chemical Engineering for Chemists w Laboratory Safety w Methods Development, Validation Procedures, and Regulatory Compliance Issues w Pharmacokinetics and Pharmacodynamics: Principles and Applications in Pre-Clinical Drug Development w Project Management for Technical Professionals w Statistical Analysis of Laboratory Data w Structure Based Drug Design
december Houston, TX | December 5 - 9 w Chemical Engineering for Chemists w Dispersions in Liquids: Suspensions, Emulsions, and Foams w Experimental Design for Productivity and Quality in Research & Development w How to Develop Validated HPLC Methods: Rational Design with Practical Statistics and Troubleshooting w Laboratory Safety & Health w Polymeric Coatings w Practical and Applied Gas Chromatography w Recent Developments in Organic Synthesis
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2011 Short Courses Calendar continued Webcasts Introductory w Beaker to Barrel: Chemical Engineering for Chemists w Chemistry for Non-Chemists w Ecological Impact of Chemicals w Effective Technical Writing
Lecture/Laboratory Courses Gas Chromatography: Fundamentals, Troubleshooting, and Method Development Chicago, IL w Late Spring, Late Summer, and Fall.
w Fourier Transform Infrared Spectroscopy
High Performance Liquid Chromatography: Fundamentals, Troubleshooting, and Method Development Chicago, IL
w FTIR Sample Preparation
w Late Spring, Late Summer, and Fall.
w Essentials of Modern HPLC 1: Fundamentals and Applications w Essentials of Organic Chemistry
w Gas Chromatography Basics w High Performance Liquid Chromatography Basics w Introduction and Use of Standard Methods for Environmental Regulatory Analysis and Compliance w Introduction to Process Analytical Technology w Mass Spectrometry Basics w On Line Monitoring for Environmental Compliance w Preparing Perfect Scientific Presentations w Principles of Analytical Chemistry w Quantitative Spectroscopy: Theory and Practice w Toxicology for Chemists
Polymer Chemistry: Principles and Practice Virginia Tech, Blacksburg, VA w March 13-18 w August 7-12 w December 4-9
Fundamentals of Polymers and Interfaces for Adhesives, Composites, and Sustainable Structures Virginia Tech, Blacksburg, VA w Late September 2011
Advanced w Computer Simulation of Reactive Flows w Essentials of Chemical Kinetics w Essentials of Modern HPLC 2: Practice, Operation, Troubleshooting and Method Development w Patent Law Fundamentals w Pharmacokinetics and Pharmacodynamics for Chemists w Pharmacology for Chemists in Drug Discovery w Polymorphism in Organic/Pharmaceutical Systems w Principles of Analytical Chemistry II w Stimuli-Responsive Polymeric Films and Coatings w Ultra-high-pressure LC (UHPLC): Concepts, Practices, and Issues and How to Get Started
On Demand w Across the Spectrum: Infrared Spectral Interpretation
Custom Training Can’t travel? Have a large group that all want to take the same course? ACS Courses can even be scheduled for on-site presentation at your company or organization. The course content can be customized to meet the needs of the sponsoring organization. Contact us at
[email protected] for more information.
Join our mailing list and be notified about new courses in 2011 at www.ProEd.acs.org/emailme Questions? www.ProEd.acs.org/2011
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ACS Leadership Development System Building Skills, Creating Leaders
Your future depends on your leadership capabilities. Take ACS leadership courses at the 2011 Spring and Fall national meetings to help you become a more valuable contributor to your organization as well as to the Society.
ACS Leadership Courses Skill Categories
Level
Basic
Personal Capability
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The ACS and You
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Running Productive Meetings
Engaging and Motivating Volunteers
Understanding Members’ Interest
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Extraordinary Leaders In-Person Courses
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ACS Spring National Meeting Anaheim, CA – March 27-31, 2011
ACS Fall National Meeting Denver, CO – August 26-31, 2011
w Engaging Colleagues in Dialogue – improve your
w Engaging and Motivating Volunteers – gain
one-to-one communication skills. w Coaching and Feedback – learn a proven process, and gain a hands-on opportunity to coach others. w Leading Change – learn a step-wise process to lead change and guide teams and committees for greater results. w Leading Without Authority – Learn practical tools to help you gain cooperation without formal authority. w Strategic Planning – improve your understanding of the strategic planning process and develop a plan that aligns with the ACS Board of Directors’ strategic goals.
tools to enlist others and make their assignments professionally rewarding, so they will participate in future assignments. w Fostering Innovation – learn a systematic and proven process to generate ideas and stimulate innovative thinking. w Collaborating Across Boundaries – learn strategies and tools to make collaboration more productive. w Developing Communication Strategies – get introduced to executive level communications and learn how to skillfully communicate in an interesting and compelling manner.
Register Today! Go to www.acs.org/leaderdevelopment to enroll, and obtain detailed course descriptions, fees, and schedules. The 4-hour in-person courses are available at National and Regional Meetings. The online courses are available 24x7 – anytime, anywhere. Unemployed ACS Members: Buy one online course for $25, get three FREE. All 4-hour facilitated courses are $25 each.
Scholarships are available for facilitated courses and the Extraordinary Leader course only. Scholarships are not applicable for online courses. For more information www.acs.org/leaderdevelopment
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LAyOFFS, COSt rEDuCtiONS, MArKEt CHALLENGES – tHE PrESSurES ON EVEryONE iN tHE WOrKFOrCE ArE At A PEAK. HOW CAN yOu AS A SCiENtiSt uP yOur GAME?
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We’re looking for more wellrounded individuals these days, Not just solid technical skills but communication, collaboration, and similar skills people need to succeed. Employer
Introducing the ACS-Harvard online courses – a suite of forty-two self-paced, online courses that you can take anytime, anywhere.
Go to www.acs.org/harvard to enroll. unemployed ACS Members: buy one online course for $25, get three FrEE. business Essentials w Budgeting w Capitalizing on Change w Creating a Business Case w Finance Essentials w Focusing on Your Customer w Implementing Innovation w Leading and Motivating w Making Business Decisions w Managing Crises w Managing for Creativity and Innovation w Marketing Essentials w Preparing a Business Plan w Project Management w Solving Business Problems Strategy Essentials w Implementing Strategy w Measuring Business Performance w Thinking Strategically Working with teams w Keeping Teams on Target w Leading a Team w Working with a Virtual Team
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Instead, Visconti and Florman suggested a selection of other ZP3 amino acids that might anchor the sperm-recognizing sugars. And with a nod to Dean’s results, they suggested that sperm can only access this sugar on ZP3 if ZP2 is not yet chopped up. Then, at the end of October, Jovine published in Cell an X-ray crystallography structure of ZP3 at 2 Å, the first ever of a complete egg-coating protein and the result of five years of effort (DOI: 10.1016/j.cell.2010.09.041). The work revived elements of the initial textbook model, wherein sperm recognize sugars on the egg’s ZP3 protein.
CELL
JOVINE’S WORK “is a major breakthrough in the pursuit of mech-
anisms involved in mammalian fertilization,” Wassarman wrote in an associated commentary (Cell, DOI: 10.1016/j.cell.2010.10.013). “It’s been a very exciting time for our field,” Visconti says of both papers. In Jovine’s structure, a threonine residue carrying a disaccharide sits in a flexible region of the protein that sperm can easily access. Also near the sugar in the three-dimensional structure is a handful of amino acid residues that three decades of biochemical experiments have suggested may additionally play roles in sperm ENCOUNTERS OF THE FIRST recognition, Visconti says. “What’s really exKIND This protein citing about this structure is that it reconciles anchors a sugar a lot of different biochemical data that sperm out there” by showing the exisrecognize on an egg’s protective tence of a binding patch on ZP3, coat. Jovine adds. Jovine’s collaborator, Tsukasa Matsuda at Nagoya University, in Japan, then replaced the sugar-bound threonine with an alanine, which cannot anchor any sugars, and did sperm-binding assays. He found an 80% drop in the ability of sperm to bind. “This suggests that the sugar on the threonine is a sperm-binding site,” Jovine says. He is quick to point out that ZP2 is probably also involved in sperm binding. “I wouldn’t be surprised if evolution has introduced a bit of redundancy into the fertilization process,” he says. “It’s very dangerous for a species to rely on a single binding site.” If this were the case, then a single mutation could wipe out the next generation. As researchers continue to home in on the way—or ways—that sperm and eggs find each other, a few experiments are clearly waiting to be done, Visconti says. For example, to conclusively prove that ZP3 and its threonine-attached sugar is an essential docking site for sperm, mice engineered to lack this amino acid should be infertile, Visconti adds. It’s unclear whether Dean, who reported similar experiments in the Science paper, will pursue the question, because he refused several requests for interviews. For Jovine, the next step is to try crystallizing ZP3 with a selection of proteins located on the sperm head—of which there are about a dozen candidates. These experiments will certainly shed light on the mechanism of fertilization, but they aren’t likely to sate researchers’ appetite to learn more about this first milestone of life. ■ WWW.CEN-ONLINE.ORG
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