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Stanford, CA, United States

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Twenty years ago, I wrote a piece on laboratory flexibility. At the time, flexible lab casework was a relatively new concept, but now movable lab furniture is ubiquitous throughout the industry and flexibility is imperative for all owners. So, I thought it would be a good time to go back and revisit the topic, dig a little deeper than just lab furniture and overhead service panels and see what truly supports changing research needs. Research labs need to be able to adapt to change. Science is changing, new equipment is being developed, and funding priorities shift, so modern labs must incorporate some degree of flexibility to deal with this. You start with what are the limits of what you can achieve in your lab. What is a flexible modification and what is a fundamental redesign. How far can you bend your facility before it breaks? Let's face it—in most labs, probably 80 percent of the flexible features in lab casework never get used. Movable tables never get moved, adjustable shelves never get adjusted. This isn't necessarily a bad thing … flexible casework is arguably the same cost as fixed casework, but it does suggest that it takes more than casework to make a lab truly flexible. Casework is getting more adjustable every day but in most instances any modification to the configuration or placement of laboratory casework must be done by maintenance staff or casework vendors. This makes sense as moving casework around requires getting up on ladders, lifting heavy objects and sometimes specialized tools. Some researchers will still insist on being able to do this work themselves, but isn't their time better spent doing research? Flexible labs were supposed to offer substantial savings in regards to renovation costs and in some cases we are seeing this reflected in fewer renovations, but in other cases we are seeing clients paying $250-$500/sf to renovate "flexible" labs. For example, Niraj Dangoria of Stanford said in an article about the Clark Center, a celebrated example of flexibility, "that when a new faculty member wanted to rearrange, it cost three times as much as in a typical research building." So herein lies the rub with most "flexible" labs, designers incorporated all sorts of flexible features and provisions for future capabilities, but when it came time to make changes the built-in flexibility didn't live up to the owners' expectations. It was as if no one could find the instruction booklet. What was missing was a flexibility plan. Flexibility: 1) the quality of bending easily without breaking; 2) the ability to be easily modified. A flexibility plan needs to start with what are the outer boundaries of what you are willing to have your facility be. There is a quality that we like to call robustness that we define as the extent to which a building's systems can support program changes. For a recent project for Vanderbilt University, the flexibility plan included the guideline that no floor could have more than 12 fume hoods. This didn't mean that there couldn't be more than 12 fume hoods on a floor at some later date, but it meant that accommodating more hoods would entail a major renovation that would involve adding additional duct risers and fans. The cost and complexity of the renovation would be so high that we could no longer say the facility was bending easily, it would be outside the limits of the planned flexibility. Similarly, a flexibility plan would also include limits for electrical load, cooling capacity, plumbing services, etc. anything that would cause an increase to base building systems or risers would be outside of the plan. Decreasing robustness limits a lab's flexibility while increasing robustness to accommodate a greater range of flexibility adds both construction(capital) and operating(expense) costs. So it's a tricky balancing act finding the right mix, but it's important to recognize this balance once you start planning renovations. The next question a flexibility plan has to address is who performs the work. Is it the users, maintenance staff or outside contractors? Genentech in South San Francisco developed SWAT teams of contractors who are familiar with their facilities and available on-call who can make frequent modifications, while other companies rely entirely on in-house staff. Sometimes it sounds like hooking up a piece of equipment or a lab bench in a flexible lab is as simple as plugging in your toaster at home. It isn't, but if you want users to have the ability to modify their lab environment on their own, there needs to be special attention paid to the details. Outlets and fixtures can be no higher than seven feet above the floor, adjustable height casework needs to be motorized or have a crank adjustment, connections can't require special tools or skills. These details can quickly drive up the cost of a lab fit-out. We are seeing a lot of movable elements in labs that were traditionally fixed. Movable base cabinets and work surfaces are great, but we strongly recommend against allowing users to move any equipment that may pose a hazard such as fume hoods, biosafety-cabinets and sinks (anyone who has had to deal with balancing issues or the aftermath of a sink that overflowed over a weekend knows what I mean). If you do plan on user performed changes, there needs to be a limit to what users can be allowed to do themselves (e.g. no getting up on ladders) and this then needs to be accounted for in the design. Another question that the flexibility plan needs to address is how long can a renovation take? A day? A week? Longer? Can the renovation be done while the lab is in operation or will there be down time? Obviously it will be cheaper to do the work during working hours, but if work has to be done after hours or on weekends, this needs to be factored in. Working with a client in New York City, we found that we could get a full 40-hour week by having contractors work triple shifts over a weekend because schedule and downtime concerns outweighed budget constraints. Clients ask us, "Can [you] design a single lab type that will meet all of [our] needs?" The answer is yes, but it would be prohibitively and unnecessarily expensive. Instead, we recommend that they pull out their core spaces, their specialized equipment rooms, microscope suites, robotics labs, etc. The spaces may have specialized utility demands, temperature and humidity requirements or maybe just the need to be darkened. These spaces have very specialized equipment where the typical utilities or conditions might not be appropriate. Providing flexibility for these spaces means providing enough utilities and infrastructure so that when the spaces need to be renovated, the work can be limited to within a single lab. Some of the most flexible labs that we have seen didn't utilize a lot of movable casework, but rather identified a zone of spaces that were close to the necessary utilities and could be easily renovated without disturbing adjacent spaces as equipment changed or needs shifted. So at the end of the day, I want you to think of flexibility as more than just a matter of casework on wheels and overhead service carriers. It's a plan that starts with initial design and carries through for the life of the building. Over the years, we have worked with numerous clients to develop their flexibility plans, whether they had a "flexible" lab or not. But whatever the status of your current lab, a flexibility plan now will allow you to meet changing needs in the future while reducing your renovation costs and your lab downtime.

Beltrao P.,University of California at San Francisco | Beltrao P.,California Institute for Quantitative Biosciences | Albanese V.,Clark Center | Kenner L.R.,University of California at San Francisco | And 14 more authors.
Cell | Year: 2012

Protein function is often regulated by posttranslational modifications (PTMs), and recent advances in mass spectrometry have resulted in an exponential increase in PTM identification. However, the functional significance of the vast majority of these modifications remains unknown. To address this problem, we compiled nearly 200,000 phosphorylation, acetylation, and ubiquitination sites from 11 eukaryotic species, including 2,500 newly identified ubiquitylation sites for Saccharomyces cerevisiae. We developed methods to prioritize the functional relevance of these PTMs by predicting those that likely participate in cross-regulatory events, regulate domain activity, or mediate protein-protein interactions. PTM conservation within domain families identifies regulatory "hot spots" that overlap with functionally important regions, a concept that we experimentally validated on the HSP70 domain family. Finally, our analysis of the evolution of PTM regulation highlights potential routes for neutral drift in regulatory interactions and suggests that only a fraction of modification sites are likely to have a significant biological role. © 2012 Elsevier Inc. Source

Mackanos M.A.,Stanford University | Mackanos M.A.,Stanford Infrared Optics and Photomedicine Center | Mackanos M.A.,Clark Center | Helms M.,Stanford University | And 6 more authors.
Journal of Biomedical Optics | Year: 2011

The cytoprotective response to thermal injury is characterized by transcriptional activation of "heat shock proteins" (hsp) and proinflammatory proteins. Expression of these proteins may predict cellular survival. Microarray analyses were performed to identify spatially distinct gene expression patterns responding to thermal injury. Laser injury zones were identified by expression of a transgene reporter comprised of the 70 kD hsp gene and the firefly luciferase coding sequence. Zones included the laser spot, the surrounding region where hsp70-luc expression was increased, and a region adjacent to the surrounding region. A total of 145 genes were up-regulated in the laser irradiated region, while 69 were up-regulated in the adjacent region. At 7 hours the chemokine Cxcl3 was the highest expressed gene in the laser spot (24 fold) and adjacent region (32 fold). Chemokines were the most common up-regulated genes identified. Microarray gene expression was successfully validated using qRT- polymerase chain reaction for selected genes of interest. The early response genes are likely involved in cytoprotection and initiation of the healing response. Their regulatory elements will benefit creating the next generation reporter mice and controlling expression of therapeutic proteins. The identified genes serve as drug development targets that may prevent acute tissue damage and accelerate healing. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). Source

Mackanos M.A.,Stanford University | Mackanos M.A.,Stanford Infrared Optics and Photomedicine Center | Mackanos M.A.,Clark Center | Contag C.H.,Stanford University | And 2 more authors.
Journal of Biomedical Optics | Year: 2011

Induction of heat shock protein (Hsp) expression correlates with cytoprotection, reduced tissue damage, and accelerated healing in animal models. Since Hsps are transcriptionally activated in response to stress, they can act as stress indicators in burn injury or surgical procedures that produce heat and thermal change. A fast in vivo readout for induction of Hsp transcription in tissues would allow for the study of these proteins as therapeutic effect mediators and reporters of thermal stress/damage. We used a transgenic reporter mouse in which a luciferase expression is controlled by the regulatory region of the inducible 70 kilodalton (kDa) Hsp as a rapid readout of cellular responses to laser-mediated thermal stress/injury in mouse skin. We assessed the pulse duration dependence of the Hsp70 expression after irradiation with a CO 2 laser at 10.6 μm in wavelength over a range of 1000 to 1 ms. Hsp70 induction varied with changes in laser pulse durations and radiant exposures, which defined the ranges at which thermal activation of Hsp70 can be used to protect cells from subsequent stress, and reveals the window of thermal stress that tissues can endure. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). Source

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