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From cloning genes to directing X-rays: Face to Face with Nishant Kumar Varshney

in Face à Face by

Dr Nishant Kumar Varshney is working as a Beamline Scientist on an Indo-Italian Macromolecular Crystallography beamline XRD2 at Elettra Sincrotrone, Trieste, Italy, which will be open to Users in start of the 2017. The Career Support Group (CSG) for STEM PhDs caught up with him about his career and experience while working in an unconventional postdoctoral career of a Beamline Scientist after a PhD in Structural Biology.

He did his bachelors in Chemistry from DU and Masters in Marine Biotechnology from Goa University in 2005. Completed his PhD in 2013 from Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India on structure-function relationship of three enzymes that has industrial and therapeutic applications. During his PhD, he received Commonwealth Split-Site Scholarship to work for an year in York Structural Biology Laboratory, University of York, UK, where he developed his interest in the field of Structure Based Drug Discovery field.

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In Nishant’s (NKV) words, “First, I would like to thank Abhinav Dey (AD) for adding me to CSG group and now giving me this opportunity to share my thoughts about new Indo-Italian joint venture at Elettra Synchrotron, Trieste, Italy which we Inaugurated last month.”

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(XRD2 Beamline; Picture source: NKV)

AD: During your graduate school, when did you realize you wanted to try a different research-based career than conventional postdoc?

NKV: Actually the thought and the opportunity came after the PhD, when I was working as Research Associate (RA) in National Center for Cell Science (NCCS), Pune. During my PhD, I was working both at the bench (cloning, expressing, purifying and setting up protein for crystallization) as well as collecting data at our home source for my proteins and sometimes helping other collaborators. Like most of the graduate students, I dreamt of getting a conventional post doc position abroad and coming back after few years for some decent permanent position in India. It was during RA-ship, that I saw the ad for a Beamline Scientist position at the new Indian beamline at Elettra. I thought of it as a good opportunity to not only learn about the working of beamlines but also having plenty of time to play and learn with data collection strategies to get best out of your protein crystals. Moreover, the idea of helping different users with different projects and, if possible, making some worthy contribution to their projects excited me too.

AD: What is your typical work day like?

NKV: Most often our day starts with a black filter coffee at 9 🙂 and ends around 6pm. Currently, we are at the final stages of commissioning the beamline and implementing an automated instrument on the experimental table. Since working at the beamline is a first time for me, my work schedule usually revolves around my local supervisor and Head of our group, Maurizio. We help our supervisors with the work and learn out of it. Everyday there is something new to learn. We set small targets with deadlines and sometimes we work till late to meet those deadlines. Also being an industry, there are many other usual administrative/non administrative appointments also to be taken care of.

AD: Do you think having a PhD was an advantage for you in the current job?

NKV: Yes. Experience and a degree in structural biology were the essential educational qualifications for this job. I was brought into the field of X-ray diffraction, protein crystallization, three-dimensional structures etc. in practice during my PhD only. Having hands-on experience with these techniques and a visit to a Beamline in Diamond, UK during my Commonwealth Scholarship tenure gave me experience and confidence to apply for this job. Some technical terms and what’s behind the walls of Experimental Hutch was totally new to me in the beginning but I think I am getting better day-by-day.

AD: How was the transition from a bench to a synchrotron?

NKV: I would say transition was not that easy. Coming from enjoying a mostly wet lab, handling buffers/proteins and transitioning to the technical aspects of a synchrotron where I was expected to understand as well as install beamline components, alignments, installing vacuum etc. was initially too much technical for me. Mathematics has not been my strongest subject so I am still trying to get better with the numbers.

AD: What would you recommend as first steps for students/postdocs interested in pursuing a fellowship in handling this kind of job?

NKV: If one is coming to synchrotron as a user, I would say, apart from having familiarity with data processing programs and knowing your proteins, you need not to worried about what’s behind the walls of Experimental Hutch. Beamline staff should teach you how things work at the Experimental table and how to collect data. But if someone wants to be a Beamline Scientist or a Beamline Postdoc, first step is to develop your love for the technical aspects of a beamlines. Brushing up your Physics or say Biophysics will also help you to understand your work. It is also important to keep in mind that it is not a 9-5 job and you should be ready to devote long days sometimes.

AD: Having gone through interviews as an applicant yourself, what are a couple of things that could help a PhD standout from the crowd?

NKV: Especially for a job at the Beamlines, working knowledge of the beamline, however little it may be, through regular visits to the synchrotron for data collection and processing the data on your own will make you stand out. Familiarity with different programs for data collection to structure deposition will help you for the job. Apart from that, one should enjoy working with the users and be ready to help them to sort out the technical as well as practical problems outside the normal office hours.

AD: Was there anything (positive or negative) that you were surprised about this job/profession that you didn’t expect until you were in it?

NKV: As a matter of personal opinion, anyone who starts the unconventional career, will wish to have a sense of stability in his/her tenure. As I am working in an Italian Industry, as a visiting Scientist on an India-funded project, there is always an insecurity regarding the length and timing of the next extension. Moreover, the absence of funds available for in-house research and for attending/presenting work in the conferences was not what I expected.

AD: Please tell us about the new Indo-Italian venture and what do you foresee of this collaboration for the development of science in India?

NKV: Till the date, India is either renting beamtimes for macromolecular crystallography e.g. BM14 beamline in ESRF or funding visits to other beamlines of the world. This is the first time when India is a partner right from the design, construction, commissioning and maintenance of two beamlines at synchrotron. The XRD2 and Xpress beamlines are a part of a scientific partnership between India and Italy under a project administered through the Indian Institute of Science (IISc) at Bangalore with financial support from Department of Science and Technology (DST), Govt. of India and Elettra Sincrotrone,Trieste. The Xpress experimental station has been constructed to study the structure of materials under high- pressure using the technique of X-ray diffraction of samples subjected to the action of two diamonds that can exert higher pressures to 50 GPa. In this way the researchers will be able to access the possibility of synthesizing new superconducting materials, harder and more resistant. This beamline will also be applied in other areas, such as mineralogy and geophysics. XRD2 is a dedicated beamline to determine three-dimensional structures of proteins and biological macromolecules with application in biology, medicine, pharmaceuticals and biotechnology. XRD2 is an highly automated and tunable beamline with state of the art instruments which will allow to collect faster X-ray diffraction data from protein crystals in highly automated way better than collected using home source. With 50% share in the project, now Indian crystallographers and High Pressure diffraction groups will have plenty of beamtime accessible to them. Once the proposal has been accepted, DST will provide the travel and daily cost funds.

AD: What are the career possibilities after being trained at the cutting edge of your field?

NKV: The field of macromolecular crystallography is still in a developing stage. There is lot to explore and develop in the field right from the data collection step to relate the structure to its function. With the experience at the synchrotron, prospects of developing your own research in the field are always open. Working in Pharmaceuticals Industries mainly involved in Structure based Drug Discovery is another option. With all the knowledge of the structural biology, a career in academics is also a possibility. Moreover, with the advent of Free-Electron lasers and new developments in alternative techniques, three-dimensional structure determination of macromolecules using serial crystallography and Cryo-Electron Microscopy and Cryo-Imaging techniques are the new open fields where experience in structural biology is a desirable qualification.
I hope, these facilities will be very beneficial to our Indian researchers.

 

 

Nishant Kumar Varshney was interviewed by Abhinav Dey. Abhinav is a postdoctoral fellow at Emory University and a Young Investigator Awardee from Alex’s Lemonade Stand Foundation for Childhood Cancer. He is also the co-founder of PhD Career Support Group (CSG) for STEM PhDs and ClubSciWri

(https://www.linkedin.com/in/abhinavdey)

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This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Featured image source: Pixabay

The different hats of technology transfer officers

in Entrepreneurship/Sci-IP by

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With the establishment of Bayh Dole Act in 1983, US universities started establishing “Technology Transfer Offices”, whose main job was to evaluate inventions coming out of their laboratories. This helped universities to protect their intellectual property (IP) and license it out to startups or established companies. Technology transfer begins as soon as inventors disclose their technology to technology transfer offices. A technology transfer officer then wears different hats- an inventor’s, an attorney’s, an entrepreneur’s, an industrialist’s or a consumer’s to weigh various aspects of the technology before he/she consents to file a patent. As simple as it sounds, it requires a sound knowledge of the science involved and the rules and laws of patent prosecution. It also requires the business acumen needed to license a technology after filing a patent. Let us go through these steps one by one:

Determining prior art: The first and the most important hat worn by a technology manager is that of a patent agent. He/she asks the most important questions on the disclosed technology that a patent office will also ask: Does the technology have “utility” in the real world? Is the technology “novel”? Given all the previous knowledge or literature in the field, is the technology described by the inventor “obvious”? A patent will be granted by a patent office only if the answer to the first two questions is affirmative, and the answer to the third question is negative. Based on literature and patent database searches for the disclosed technology and judgment from experience, technology transfer officers decide whether to proceed forward with the technology and file a patent.

Freedom to operate (FTO): Wearing an attorney’s hat, the tech transfer officer asks another crucial question: Assuming that a patent is issued for the disclosed technology, can the owner or licensee of the patent practice the invention without infringing upon other patents? In other words, how much “freedom to operate” does the patent actually confer to its inventor/owner/licensee when compared with other patents that have been granted in the same area. A patent that cannot be practiced is as good as not having the patent. It is like investing in a dead technology. No business will buy or license out the technology. Patent prosecution being a very expensive process, a technology transfer officer evaluates the FTO very carefully to decide whether or not to invest university’s money to protect the technology. In my future blog, I will discuss FTO in detail.

Market: The next hat that a technology transfer officer wears is that of a marketing analyst. A tech transfer officer is not only involved in protecting the IP but is also instrumental in supporting the development of the technology. The whole idea of protecting the technology is to incentivize the companies to license out the technology from the university to make it useful to the society. To attract industries to invest in the technology many important questions are asked in advance: 1. What is the current market for the technology? 2. What is the market landscape (what other companies are involved in the technology space?) 3. If the technology enters the market, how much market penetrance will it get? In other words, will the industry see the return of investment if they license the technology from the university? Stage of development: A crucial factor in marketing university-owned technologies is to gauge the stage of development of the technology. Most of the university-based technologies are very embryonic or in other words, very early-stage technologies. Such technologies, especially in biotechnology, need a lot of investment from companies who are licensing it, both in terms of money and product development. Remember, an issued patent has a term of 20 years from the date of filing in

Stage of development: A crucial factor in marketing university-owned technologies is to gauge the stage of development of the technology. Most of the university-based technologies are very embryonic or in other words, very early-stage technologies. Such technologies, especially in biotechnology, need a lot of investment from companies who are licensing it, both in terms of capital and time investment. Remember, an issued patent has a term of 20 years from the date of filing in USA. A technology that requires a long incubation time will eat up the patent term (number of years of the patent rights). Losing the patent term means losing the competitive advantage. Therefore, the technology transfer officer needs to ascertain that there will be sufficient patent term remaining for the company, to recover its invested dollars and generate a considerable return of investment on the product.

Tradeoff analysis: One of the primary objectives of technology transfer offices, as I have already mentioned, is to see the university technology get developed into a product that is directly useful to the society. Therefore, the tech transfer officer evaluates pipeline products of companies, their business and development plans, their market share and capital as well as their past performance in developing the licensed technologies. The question whether the technology is suitable for a startup or an established companies is very crucial. A startup will have a vested interest in developing a technology. Therefore, it will have a focused approach towards the development of the product. In the case of established companies, they will have several products in their pipelines. Therefore, their focus, and hence, the development plan my change with changing priorities that is heavily shaped by the market. At the same time, startups are risky, and their product development pipelines are not as well charted out as an established enterprise. Therefore, an important challenge for tech transfer officers is to do a tradeoff analysis to narrow down the companies that will provide the best opportunity for the technology to get developed into a viable product.

Technology valuation: This is perhaps the most difficult part of the technology transfer process in the universities for which there are no easy answers. In general, the technology transfer officers rely on past deals (also known as comparable deals) for similar technologies and market analysis to come up with a value. There are complex quantitative ways to estimate the cost of the product 5-10 years from the present day for a thorough evaluation. One can easily imagine the difficulty in predicting the market a decade in advance. The two most important aspects of valuation are license issue fee and royalty. The latter is most important for universities, as it is their return of investment for their innovation. It is through royalties that universities can pump back money into the basic research and infrastructure. They can also incentivize inventors by giving them a part of the royalty.

Salesman: A tech transfer officer also needs to be an excellent salesman. Like a prudent salesman the officer has to win the best possible deal (in terms of royalty from the sale of the technology (also known as consideration) and due diligence (DD) terms for the technology development) for the universities. This is the most challenging hat worn by a tech transfer officer. It starts when a company shows interest to license a technology for making, using and selling it as a product. The tug-of-war involved in coming to a perfect term for a licensing deal is a thesis on its own. It will be sufficient to stress that this step requires the wizardry of a technology transfer officer to win a profitable deal for the university to support everything that a tech transfer office stands for. During the negotiation process, the officer always makes sure that the interest of the university and its IP is given the supreme interest. Once, the negotiation is done, the deal is formalized in a license agreement and is then bound by the law of the state.

Police Officer: Following license agreements, tech transfer officers monitor the strict DD terms. DD is very crucial for technology transfer officers, because it acts as an instrument to make sure that the technology gets developed in a timely manner. Breaching DD leads to termination of the license agreement.

The final goal is to see that the technology gets developed and is transferred to the masses for their consumption, thereby advancing the society through cutting-edge science and technology.

Ananda Ghosh

https://www.linkedin.com/in/ananda-ghosh-3238a716

How to create and measure innovation?

in That Makes Sense by

“Innovation” is THE buzz-word of today!

Everyone wants to label their companies as innovative, hire innovative people, create processes to induce innovation and be the next big innovator! But how does one really ‘innovate’ and how do we quantify innovation?

Sarah Kaplan, professor at the Rotman School of Management at the University of Toronto came up with an interesting answer that you might not have expected.

It is generally thought that brain storming with people from diverse knowledge backgrounds is a great way to come up with new ideas. In their paper, Kaplan and colleagues show that while combining different disciplines does lead to novel ideas, there is another equally important way that innovation works. In-depth knowledge in a field is required to understand the anomalies within the field, which can then lead to novel ideas.

“We find that, counter to theories of recombination, patents that originate new topics are more likely to be associated with local search, while economic value is the product of broader recombinations as well as novelty.”

Interestingly, breakthrough innovations were more likely to result from searches within a domain but economic value was a result of novel innovations arising from a combination of diverse ideas. However, such patents were very rare making up only 1% of the dataset.

“Patents that were both novel and had economic value were the most valuable. And that was only about 1% of the total patents.”

At this point, most researchers must be nodding in agreement “I had thought so”. What was the most surprising thing for me, though, was the way they measured “novelty”. In scientific literature as well as the patent world, innovation is measured as a direct function of citations. Even though most of the scientific community has rejected the idea of the journal impact factor as a way to measure the quality of a scientific article, the next best measure employed is the number of citations for the article itself. Thus, a patent or scientific paper that get highly cited is considered superior and thus a breakthrough innovation.

“What we found in our study is, in fact, that most of the patents that do get highly cited are not necessarily novel.”

In this study, the authors used a different metric to examine patents from the field of nanotechnology. A computer science and natural language processing (NLP) method called topic modeling that uses “a bag of words, a body of text, …and it infers from that body of text by the co-location of all the different words, what are the key underlying topics in the data”  was employed to determine if novel ideas were being developed. Interestingly, the patents that had high level of citations were not necessarily novel.

This is an interesting revelation, and something that scientists should also consider while judging the quality of literature. The entire reward system in science is largely based on publications and the feedback from citations. This generates ‘hot’ topics that many scientists work on, read about and cite, thus creating a research bubble. In such an environment, other fields of potential interest have difficulty to gain exposure and citations. Researchers flock towards hot topics, which can hinder the overall progress of science.

This generates ‘hot’ topics that many scientists work on, read about and cite, thus creating a research bubble. In such an environment, other fields of potential interest have difficulty to gain exposure and citations.

Kaplan and her group plan to delve deeper into how innovation works by studying novel ideas in different fields. It would be interesting to see what insights they can bring!

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About the author: Czuee has a PhD from the University of Lausanne, Switzerland and Masters from IIT Bombay. She has previously worked at IISc-Monsanto collaboration and as a patent analyst at Evalueserve. Apart from her research on proteins involved in brain signalling and diabetes, she is interested in scientific communication (czuee.wordpress.com), entrepreneurship and runs a webcomic (http://gradschoolmuse-icals.thecomicseries.com/).

Photo source: Forbes.com

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