Gianpaolo Rando

Scientist and blogger Gianpaolo Rando is BioData Blogs Featured Scientist for the month of April. Read about trends in the development of reporter genes in his blog, reportergene.com

Tell us about your first encounter with science
I was 12: I was a strong reader and a loyal fellow of the civic library. Books being the main source of my knowledge, I thought everything in the world had already been discovered. At the beginning of the school year, my new science teacher introduced a small aquarium to the classroom. He put in a mug full of water from a waterhole and asked the class to observe daily the little water box for two weeks. Life immediately developed and gradually faded when the food resources started to get out. I learnt the basics of ecosystems by direct observation. This was my first encounter with science and the first time I realized that knowledge can be obtained in real-time without need for a book. I asked myself: do you want to only be a reader or do you want to take part in the race toward knowledge? It took 10 years of ‘boring’ book-reading before I really started taking part on my own bench with tubes and pipettes.

What made you choose a scientific career?
My curiosity. I’m curious, pathologically curious. I’ve always wondered how the world runs, and particularly the way living things work. What are the mechanisms and what are the dynamics? Choosing a scientific career was very natural.

What is your current area of research?
I received a M.Sc. in Biotechnology and a Ph.D in Pharmacology at the University of Milan (I’m a former Pharmacologist). I’ve always been fascinated about how small molecules can influence our physiology and our mind. My interest particularly concerns so-called ‘nuclear receptors’, these are proteins that are able to directly sense the presence of small chemicals (i.e., hormones, metabolites, drugs) and to consequently modify gene expression by binding on selected DNA sequences on gene’s promoter regions. Recently, I joined the Center of Integrative Genomics at the University of Lausanne where my current research focuses on the differences in nuclear receptor signaling between males and females.

Why did you decide to start a scientific blog? What reactions did you receive?
It was an experiment. Four years ago I wondered which part of the world was most intellectually active in one particular field of molecular biology (the development of reporter genes). Of course pubmed can give some answers, but I wanted to know not only which labs were publishing most, but also about the public: Where the readers were? Where the discussion was? What was more popular: luciferase or GFP? So I registered reportergene.com and I started commenting on papers dealing with new technologies involving reporter genes. The idea was to resolve the IP address of the visitors and obtain a map of niches interested in the development of genetically-encoded approaches. The blogging platform was chosen because of its simplicity, but at that time I was not thinking of it as my blog.  One year later I gradually realized that a scientific blog was an opportunity of immediate communication for a scientist. Young researchers can work three years or more before getting into a publication, and probably never being contacted about their work (if they aren’t the corresponding author). Despite the vastness of the scientific community, PhD students and postdocs are still confined to their benches with limited social connectedness: you can speak every-day with your 10-20 lab-mates about your research or, once a year, try to catch some of the 100 conference attendees toward your poster. This is poor communication. In this sense, a blog is a short-circuit: you can debate your arguments every week with thousands of readers: writing a post takes the time of a coffee, but gives you immediate feedback on the topics you are interested in. You are still ‘at the bench’ working full-time on your project but once a week, your coffee break takes a world-wide dimension, and you immediately feel the world wide web of the scientific community.

Your last paper introduces a new method to classify drugs, what are the current problems in drug classification?
There are several ways to classify a drug (i.e., chemical composition, etc), one criteria concerns drug action and it is based on a theoretical framework which dates at the middle of last century. In very simple words, if a drug activates a biological effect is an AGONIST. A second drug that competes with an agonist, preventing the effect, is an ANTAGONIST. Today, because of our better understanding of the complexity of intracellular signalling, this definition becomes of difficult application. Most of the drugs act by binding to a cellular receptor: upon binding, drugs ‘activate’ the receptor, initiating the signaling cascade responsible for the biological outcome; we know that a single drug can induce different signaling cascades, and this ability may change significantly with respect to the tissue where the drug is acting and the time after drug administration. In short, a candidate drug can be agonist in the first week of therapy and suddenly may became antagonist (with obviously deleterious side effects!). Likely, such a candidate drug would be discarded in the drug development pipeline: in fact, it is common for unforeseen toxic profiles to be discovered late in the pipeline, already at the level of clinical studies in humans. This is unwanted: a failure of a clinical study is a great loss for a pharma-company. In conclusion, pure semantical problems about classifying drug action may contribute to stagnation in the biomedical economy other than being a potential hazard for human volunteers.

What is the current model of understanding drug effects over time?
Current models belong to a discipline called Pharmacokinetic (PK) which studies the drug distribution in the body over time. With PK we can predict the presence of the drug in a particular organ, however, we don’t get any information about the pharmacological effect. Drug action is studied by a second discipline called Pharmacodynamic (PD). My PhD dissertation deals with the possibility to introduce new dimensions (space and time) in PD studies by monitoring drug action on living ‘luciferase reporter-mice’ developed by my PhD mentor: Adriana Maggi. These animals start glowing when and where a drug is active: for the first time in the history we can study drug effects in a safe living mammals without  the need to kill them. We are developing the technology to follow drug activity in different anatomical areas several times in a day for long period of times (months) without actually killing any animals. This new knowledge would have the power to disclose potential side-effects before getting into clinical studies, with clear social, ethical and economical benefits for men (and mice also!).

Why a SERM was chosen as a model?
Selective Estrogen Receptor Modulators (SERMs), were conceived for post-menopausal hormonal replacement therapy to avoid estrogen unwanted effects on breasts while retaining their beneficial effects in other organs. As their name says, SERMs activity on the cognate receptor is ‘selective’ – this means that a SERM that blocks estrogen’s action in breast cells may activate estrogen’s action in other cells, such as bone. To date however, none of the SERMs developed appears to be provided of the ideal balance of ER agonist and antagonist activity. Because SERMs do not fall into distinct categories of agonists and antagonists, they represent a great ‘proof of concept’ to further elaborate on drug classification. Furthermore, menopause is one of those permanent conditions in which a drug is supposed to be administered chronically: the time dimension can not be further neglected.

References: Rando, G., Horner, D., Biserni, A., Ramachandran, B., Caruso, D., Ciana, P., Komm, B., & Maggi, A. (2010). An Innovative Method to Classify SERMs Based on the Dynamics of Estrogen Receptor Transcriptional Activity in Living Animals Molecular Endocrinology, 24 (4), 735-744 DOI: 10.1210/me.2009-0514

Lab Instructor and science enthusiast Joanne Manaster is this month’s BioData Blogs Featured Scientist. Follow Joanne at @sciencegoddess on twitter or on her website, Joanne Loves Science.

How did you first become interested in the science field?

I’ve just always known I would be doing science all my life. There was never a doubt and I can’t imagine anything else. Early on I thought it would be astronomy but after I broke my foot in 5th grade, I turned my attention to wanting to become a doctor. I knew scientists (researchers) existed somewhere but never had any introduction to it or considered it an option until about my junior year of college when I sat next a professor on a train. I must have impressed him because within about half an hour of meeting, he offered me a position in his lab as general help. Also, my junior year, I took a course that was a combination of cell biology and histology. I remember exactly where I was sitting and even what I was wearing when I had the sudden realization that I truly loved this material and knew that I had to use this information and learn more and more about it. After meeting the professor of that course, he soon offered me the option to help do some organizing and prep work and then ultimately help him instruct some of the lab courses. That is when I learned that I was very comfortable teaching science to semi-technical audiences, and especially good at explaining HOW to do techniques.

What is your favorite part of research and lab work? What is the worst part?

I love sharing my enthusiasm with students. I especially enjoy helping them learn lab techniques because they can see and feel concretely that they have done something, versus what they experience in theory work courses. I know I can teach anyone to do any technique I can do. Because of this, I get plenty of “knocks on my door” from engineers wanting to learn biological techniques. The worst part about lab work is when you are feeling frazzled or are not prepared to work and then everything seems to go wrong. We all have days like that!

Can you tell me a little bit about your work?

Even though I find research fascinating, I decided not to pursue that as a career goal. I was much more excited by teaching, so chose to run laboratory courses and to occasionally lecture for non-lab courses. I’ve designed multiple lab courses over the years, mostly revolving around cell biological, histological and cell culture techniques. I love to take any opportunity to visit research labs and see new techniques and ask questions so I can pass new ideas to the students. After deciding what topics need to be covered, I test protocols and make them almost foolproof. That includes finding the most useful reagents at great prices, as well as refining and writing clear instructions. Day to day, I ensure supplies are ordered, reagents are prepared and aliquoted for students. I do simple maintenance of lab equipment and find the people who can help when the problems are beyond my expertise. I handle student and administrative issues and supervise several student employees. For the cell culture and tissue engineering course, I hire a freshman to do the cleaning, stocking and sterilizing. If they are new, I have a lot of training to do. I also employ a junior or senior who has taken my course to prepare the media and other reagents as well as tend to the cells before handing them over to the students. And then I have graduate students who come in as teaching assistants and other undergraduates who help the TA with the course (activities are run in an outer lab area as well as the culture facility). For each set of employees, I provide a weekly list of responsibilities that I discuss with them. This helps keep them organized and all parties clear on respective duties. This course has a lecture component, which I love because I can share my enthusiasm over the latest findings in the area of stem cells and tissue engineering. Naturally there is a grading component and a website to maintain. In a way, it is much like running a research lab combined with the duties of teaching a lecture course. I have another course that is run much like a medical school histology class, which requires very little wet reagent prep work, but a lot of question answering and explaining of what students hope they are seeing through the microscope.

In your opinion, what is the most important quality for a scientist to be successful?

To be curious! Accept and nurture that part of yourself. Having good fine motor skills is a plus!

Can you share any tips for lab management and organization?

I had to, over the years, make compilations of recipes, protocols and instructions for EVERY aspect of the lab, from cleaning to equipment handling and troubleshooting, to reagent prep, to data keeping, to phone numbers. I find if I have prewritten calculations of commonly used volumes of reagents, I save quite a bit of time over the course of a semester. These instructions are kept online and also in binders with the pages in sheet protectors and tab dividers. If a TA or other employee is ever lost about what to do, they have the “giant notebook” to consult! The cleaning person should never feel perplexed as to what needs to be done because they can consult another binder created especially for them.

What is your next step? Where do you plan to be in ten years?

I do a tremendous amount of outreach to the local community in the form of a girls engineering camp (GAMES) as well as now being an adviser for U of I’s iGEM team. I’ve participated in the state science fair and the state and national level Science Olympiad. My international outreach includes my advisory position with the Young Scientist’s Journal International, as well as my social networking involvement on twitter, through my website and my youtube videos where I have taken to trying to discuss science in unexpected, whimsical and meaningful ways! I hope to find ways to bring my enthusiasm for science to a larger audience, and hopefully have appeal to a wide audience, ranging from children through adults, especially to those who thought they didn’t like science and surprise them that they actually can enjoy it and even understand it. I expect to have a larger presence within the new media in order to do this and possibly creating an online “channel” that contains great programming with real and accessible science, presented in interesting and entertaining ways, and especially emphasizing women’s role, but would accept a more traditional TV opportunity if it were part of a smart science show.

Hana Kucera has always had an interest in science. Kucera credits her scientific fascination to her parents who first introduced her to the observation, exploration and study of living things in their natural habitats. She graduated from British Columbia’s Simon Fraser University in 2004 with a B.Sc. in Biology. As a Master’s student at the University of New Brunswick in the fall of 2004, Kucera began her research in Dr. Gary Saunders’ lab studying the diversity of marine intertidal seaweeds of Canada using variation in DNA barcode sequences. Kucera subsequently transferred to the PhD program, where she is currently finishing the “last bits of lab work” to complete her PhD.

Seaweed studies in Saunders’ Lab require the researchers to spend three to four weeks of the summer collecting seaweeds from various parts of Canada. Kucera usually collects samples in her native British Columbia traveling around Vancouver Island. The researchers have not only traveled extensively throughout the east and west coasts of Canada, lab members have also traveled to subarctic Churchill Manitoba, located on the Hudson Bay of Canada. Seaweed collection in the subarctic is particularly interesting, according to Kucera, because it allows researchers to hypothesize about species distribution. When a species is found in both the Pacific and Atlantic Oceans, it is possible that the species crossed over via the Arctic. Additionally, the Arctic is an extreme environment for seaweed to grow, as ice scours rocks thereby providing difficult conditions for seaweed growth.

DNA barcoding has been the primary focus of the lab for the past five years. Kucera explains that there are three general groups of seaweeds – reds, greens, and browns and each type of seaweed requires a specific method for DNA extraction. While red and green seaweeds have a fairly straightforward method of DNA extraction, brown seaweed tends to have a lot of polysaccharides and other PCR inhibiting compounds that need to be removed separately, adding an extra step in its DNA extraction. After extracting DNA from the seaweed, researchers perform a straightforward PCR amplification of DNA barcode markers as well as other markers being studied in the lab. All sequencing is done on the premises, as Saunders’ lab has an in-house sequencer.

Saunders’ lab has been using molecular techniques like DNA sequencing and barcoding since it became available. In fact, Hana’s supervisor, Dr. Gary Saunders, was one of the first researchers who began to do seaweed taxonomy based on DNA sequence comparisons. Prior to DNA barcoding, seaweed taxonomy traditionally was based on morphological and anatomical characteristics of the plant. Seaweed morphology focuses on studying the general shape, color and other characteristics of the each blade visible to the naked eye. For example, a branch seaweed would have its branching pattern studied. Analyzing the seaweed’s anatomical characteristics requires the examination of internal structures, both vegetative and reproductive.

Dr. Saunders, who has been working in traditional seaweed taxonomy over the past few years, is an expert in both morphological and anatomical differences between species. “…DNA barcoding allows [Dr. Saunders] to rapidly screen hundreds and hundreds of collections and arrange them into the groups based on similarities in their DNA sequences. He then examines these ‘genetic species groups’ for morphological or anatomical characteristics unique to each group,” Kucera explains, “Whereas, if he were to visually inspect each specimen, he might not be able to detect subtle differences between specimens indicating new species or it would it would be too time consuming to sift through thousands of collections hoping to discover new species… This DNA barcoding system provides a rapid screen that gives you the first hint of where to look for new species.”

Hana had her first paper titled, “Assigning morphological variants of Fucus (Fucales, Phaeophyceae) in Canadian waters to recognized species using DNA barcoding,” published in 2008. Fucus are notoriously difficult to identify to species using morphological assessments, making them ideal test subjects for DNA barcoding. Hers was the first study that established that DNA barcoding works as well as any other molecular marker currently used to distinguish species of Fucus.

After completing her PhD, Kucera hopes to return to British Columbia, and seek a lecturer position. While, she enjoys research, Kucera prefers teaching and describes her ideal situation as being a senior lecturer at a university with outdoor education for students.

“Teaching,” Kucera explains, “provides me with rewards that are much more frequent than in research. With research you can work hard in the lab for months and then get a result that is exciting, but after that much time, some of the excitement may have worn off… Seeing the ‘light go on’ in a students mind when they understand a concept, that happens every day and it is rewarding to see students get excited about something new that they’ve learned.”

“I like science in a general sense and whenever you do research as a grad student you become this specialist in one area. However, as a teacher you have to draw from many different fields, bringing together various ideas into a more general concept. I like sharing this excitement for all different kinds of scientific ideas.”

• Find out more about The Saunders Lab

• Follow Hana’s Blog: Teach Me Science

• Follow Hana on Twitter: @teachmescience

• Read Hana’s 2008 Publication: DNA barcoding Botany, 86 (9), 1065-1079 DOI: 10.1139/B08-056