Scientists Simplifying Science

Monthly archive

March 2017

MedNess- March Mania

in Medness by

Hello and welcome to yet another exciting week of MedNess. In this March mania, we bring the news from medicine and healthcare with the greatest impact.

Tom Price justifies NIH’s “indirect” budget cuts

Secretary of Health and Human Services (HHS) defended Trump’s administration proposed National Institute of Health’s budget cuts. The Trump administration proposed $5.8 billion, about 18% cut for the fiscal year 2018. In addition to that, an addendum proposed an additional $1.2 billion cut for the current fiscal year. When questioned by both democrats and republicans about the nature of budget cuts, Price explained to reduce the “overhead” costs to streamline the system. According to the Secretary of HHS, the “indirect” cost takes up about 30% of the grant money, which could otherwise be available for research.
This came in as a second blow to the medical research community. Earlier this year, Trump administration pushed deregulation of FDA to accelerate the drug approval process. The research community did not welcome this proposal. Also, both pharmaceutical companies and insurance companies did not approve of the proposition (STAT and Science).

 

March for Science, a scientist’s view:  For our readers, “overhead” or “indirect” costs constitute of anything required for carrying out research safely, smoothly and efficiently! Some of the “indirect” costs include lab equipment, electricity, custodial services and other utilities. The list is not inclusive but clearly, emphasizes the importance of overhead charges. The budget cuts will not only affect the advancement of research but will also impact jobs and outreach of science. For non-science professionals, say, politicians, the overhead cost will include, electricity, custodial services, security, dinner, travel, etc. Again, the list is not inclusive! Of course, these expenses are required for the smooth functioning of the government. Before I wrap up the section, just a thought: yes, we need the stronger military to defend the country, but we need to ask this question, who are we protecting; the people and the Mother Nature. Therefore, we need an effective EPA and NIH. We need the healthy and clean environment and disease-free children and adults.

Amgen’s LDL-lowering drug Repatha: effective drug with good data for a bad price?
Amgen presented Phase III FOURIER results on Repatha (Evolocumab) at the 2017 American College of Cardiology conference. Repatha is an LDL-lowering PCSK9 inhibitor. Repatha targets PCSK9 proteins in the blood stream thus preventing it from binding to and breaking down LDL cholesterol receptors in the liver. The trial results were impressive. This wonder drug is believed to break down the most stubborn cholesterol. The FDA approved drug marketing in 2015 after the drug’s addition to statins reduced the LDL levels by about 63%. At the ACC, Amgen reported the outcome of long-term FOURIER trial and the results showed that Repatha reduced the risk of heart attack and stroke by 15% or more. Repatha met both its primary and secondary composite endpoint in the secondary prevention trial demonstrating superiority to statin therapy. However, analysts are not too impressed with the data and question the high price of the drug. Earlier, analysts with BioPharmInsight suggested that the high price of Repatha could be justified if the cardiovascular event risk reduction is at least 35%. Repatha has been price tagged for $14,000 annually. The trial findings and analyst’s reports will also affect insurance coverage of the drug (MedPage Today).

MedNess: PCSK9 is the hottest target in the field of cardiovascular research. While Amgen’s drug can crush the most stubborn cholesterol molecules, the investors were not impressed, or at least the stock market trend did not concede with it. After the results had been announced, Amgen’s stock price went down by 10%. However, a lot of analysts are still keeping their faith in Amgen’s stocks and considering this temporary dip as an opportunity for investment. On the contrary, the competition from other biosimilars is getting fiercer, and the dip in stock price might not be temporary after all. Other contenders in this area with Amgen, are the drugs from Sanofi and Regeneron. Both the companies are locked in a patent battle with Amgen. Another drug in the race is The Medicine’s Company’s inclisiran. Unlike Amgen’s, Sanofi’s and Regeneron’s drug, inclisiran interrupts PCSK9 synthesis. The analysts look at this drug as efficacious as Repatha but with fewer annual doses. If this assumption is correct, Amgen will have a hard time convincing insurance companies for their drug price. The best bet might be therefore to either wait or invest wisely (The Motley Fool and Seeking alpha).

FDA approves Roche MS drug Ocrevus after 3-month delay

The FDA approved Roche MS drug Ocrevus after initial delay caused by regulator’s concerns over manufacturing issues.
Ocrelizumab, becomes the first U.S.-approved medicine for the primary progressive multiple sclerosis. It has also been approved for relapsing-remitting multiple sclerosis (RRMS). Biogen’s MS drug has been used to treat RRMS. Biogen will receive up to 24% royalty on U.S. sales of Ocrevus. According to the pharmaceutical giant; Ocrevus is expected to be available for use to people within two weeks.

 

MedNess: Analysts forecast annual sales exceeding $3 billion by 2021 as reported by Reuters. After the approval news, Biogen stock fell by 2%, and Roche stock rose by a fraction. Novartis’s drug for MS treatment, BAF312, for secondary progressive MS is expected to receive regulatory approval in the first half of 2017. Until then, Roche can bask in glory  (Reuters, Investor’s Business Daily, FiercePharma).

FDA approves Tesaro Inc’s Niraparib for the treatment of Ovarian Cancer

Tesaro’s Niraprib (Zejula) gained an early approval by FDA for the treatment of recurrent ovarian cancer. Zejula is a PARP inhibitor causing DNA damage. It is a first drug in the class that can be used to treat all women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer without requiring BRCA mutation or biomarker evaluation. This is unlike the rival drug Lynparza by AstraZeneca. In addition, Zejula acquired orphan drug designation for its use in the treatment of recurrent epithelial ovarian cancer.

MedNess: According to EvaluatePharma, Zejula is one of the top drug launches of 2017 with 2022 sales expectations of $1.9 billion. Tesaro Inc’s shares were up 7.78 percent after the drug gained FDA approval (FiercePharma and BusinessInsider).

Illustration: Ipsa Jain

About the Author

Imit Kaur is a freelance medical writer, editor and an active science blogger. She pursued her PhD in Pharmaceutics and Pharmaceutical Chemistry from University of Utah. She is experienced in the field of oncology, hematology, pharmacology, nanotechnology and drug development.

Why I Left Bench Science and How I Found Science Diplomacy

in Poli-Scie by

Editor’s Note: Have you ever wanted to transition out of lab but the path seemed obscure? Don’t worry! You are not the only one! Read about Debanjana‘s first steps to “extraordinariness” and tune into her blog posts to follow her journey from lab to diplomacy. –Neha Bhutani

 

This is not the first time some disgruntled postdoc decided to write about his/her ‘break-up’ with science. Indeed, such stories have been told and retold; articles have been published arguing in favor of leaving academia as the most sensible option. However, not all of us learn from anecdotal evidence. We believe our story could be different (and don’t get me wrong, some stories certainly are). So we stay, and persevere, till the circumstances or our inner compass directs our departure. Nevertheless, I felt that an introduction to my past would help my readers follow my journey. Perhaps, another poor postdoc somewhere would identify and feel a little less lonely in his/her struggle. Therefore, despite the risk of being redundant, here I go:

I was born and brought up in Howrah, an industrial city whose inhabitants, including some of my closest friends and family, found their life purpose and contentment in their immediate surroundings. I would never know the precise reason why I never felt at home there. I was always too curious, too eager to feel the flow of life in cultures and lands far-away. To my relief, my educational path allowed me to move to Kolkata, Delhi, and eventually, Germany for my doctoral studies.

Germany… the land of ideas (and also of ‘kartoffeln, bratwurst and sauerkraut’, extensive recycling, Autobahns, Oktoberfest and Christmas markets). I exchanged the familiar dusty sultriness and chaotic vibrancy of Howrah with the verdant serenity and disciplined monotone of the crisp Hannover air. It was a love-at-first-sight. My PhD journey was something I cherished, thanks to a kind and supportive mentor and amazing colleagues. My stay in ‘Deutschland’ gave me some of my fondest memories, deepest life-lessons, and the official permission to call myself Dr. Chatterjee. In those four years, I was able to travel to more than a dozen countries. I discovered that my love for travel, languages, cultures equaled, if not surpassed, my love for science. However, I still wanted to continue in academia and I thought I was ready for the long grinding path of ‘postdoc’-ing for several years to land an elusive tenure-track position. Up, as I always am, for a new adventure, I set out for New York to start the next phase of my research career. The work pressure and ambition that ivy leagues abound in, added to the fast-paced life of the city, was a starkly contrasting experience to that of my German tryst. It took a while but I adapted, found great friends, as well as brilliant (yet helpful) colleagues. The project too seemed to be on a good track, with the work being recognized at multiple conferences, leading to a grant. However, my relationship with supervisor was already showing signs of strain. With time, things continued to worsen. It started taking a toll on my general enthusiasm for the project. Benchwork was never my forte; what intrigued and stimulated me about Science was the realm of ideas. As all of us academics know, everyday Science barely about the thrill of discovery. It is about long hours, failed experiments, unending patience for the minutiae, and coming home to a meagre paycheck. I began to dread every session spent with a multi-color flow-cytometer, or the hours spent readjusting a figure for the umpteenth time for a manuscript that would take forever to be published. I was miserable. I knew I had to change but I had always imagined my future in academia. So the path to change was almost obscure. After some soul-searching, I fathomed that I love people interaction and started applying for clinical research coordinator (CRC) roles. Many friends discouraged me saying that I would be taking several steps back. However, I needed a break. A regular job seemed the best option while I strived to figure out my future track. I was very lucky to find a position where I could split my time between working as a CRC and some benchwork as a postdoc. It was perfect.

The first few months of the new positions were a whirlwind with a flurry of new information, demanding clinic schedules, and a significantly different work culture. Apart from the clinical knowledge I imbibed, this contact with patients and health care providers offered me important insights on the impact of policy on healthcare and science (e.g. Affordable Care Act, Genetic information Non-discrimination Act, etc). In the mean time, I continued racking my brains about my future. I vacillated between day-dreams of lucrative pharma positions offering the delicious taste of affluence and the closeted yearning for a profession more meaningful.

Four months into this new life, I witnessed the political environment in USA turn topsy-turvy. The impending policy changes directly affected the research community as well as the hundreds of patients I had began to know in person. I strove to keep abreast with all the recent developments and did my best to assuage patient concerns regarding potential loss of health insurance for pre-existing medical and genetic conditions. However, I mostly felt like an on-looker with little to do to change the course of things.

The idea of science diplomacy dawned on me in manner no less than a revelation (dramatic drum beats…). One fine evening I was in a café reading ‘A bend in the River’ by V.S. Naipaul. The novel recounts the tale of a character named Indar, friend to the protagonist. Indar is a man of Indian descent, brought up in an affluent merchant family in East Africa, who later finds himself in London pursuing his dreams educational dreams. In the novel, Indar mentions a lady who had given him his first significant career advice. In his words,

“This lady had the idea that people like myself were at sea because we were men of two worlds. She was right, of course. But at the time it didn’t seem so to me–I thought I saw everything very clearly… this lady also thought that my education and background made me extraordinary, and I couldn’t fight the idea of my extraordinariness. An extraordinary man, a man of two worlds, needed an extraordinary job. And she suggested I should become a diplomat.“

I did not feel extraordinary. However, as a person who rediscovered her love of Rabindranritya in Hula, prepared garam masala-infused Paellas, and was about to pursue an undergraduate degree in Literature before changing her mind, the idea of being a person of multiple worlds really clicked with me. However, I did not see how I could be a diplomat with my background in Science. A random, off-hand search on the internet and lo and behold, I stumbled upon several articles on science diplomacy, a career track whose existence I was not even aware of.

I read with interest that the Royal Society and the American Association for the Advancement of Science had put-forward a summary of what “science diplomacy” entails. To quote Wikipedia, it refers to three main types of activities:

  • “Science in diplomacy”: Science can provide advice to inform and support foreign policy objectives.
  • “Diplomacy for science”: Diplomacy can facilitate international scientific cooperation.
  • “Science for diplomacy”: Scientific cooperation can improve international relations.

I was immediately attracted to the prospect to being able to utilize my knowledge and expertise in science to make an impact in the real world by helping shape evidence-based policies.

Since that fateful evening in mid December, I have spent hours googling for possible paths to break into the field. I have been able to gather a good amount of information, especially relevant to immigrant Indian postdocs like me. I plan to jot this information down in my next post. So, all the future science diplomat aspirants, Auf Wiedersehen!

 

 

 

 

 

 

 

 

 

About the author:  Debanjana is an Immunologist / Clinical Coordinator at Columbia University, NY.  She is passionate about traveling, dancing, and languages. She is here to share the musings of her meandering mind.

 

Featured Image Source: Pixabay

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

The Patent Chronicle

in Sci-IP by

Your weekly dose from the world of patents

 

EU ends plant patents

Decision: Under the EU biotech directive and European Patent Convention, plant varieties are no longer patentable.

Reason: Allow breeders to access varieties to breed new varieties.

Impact: All proceedings that entirely revolve around the patentability of a plant (or animal) obtained by an essentially biological process will be automatically suspended. Existing plant patents will not survive. New patents of this type will no longer be granted either.

Read more in in this link

 

India’s CSIR-Tech closes down

Decision: CSIR-Tech, the commercialization arm of Council for Scientific and Industrial Research (CSIR), India closes down. CSIR tech had 4,500 Indian and 8,800 foreign patents filed.

Reason: No revenue from patents, although several patents have been licensed.

CSIR director commented that most of CSIR’s patents were “bio-data patents”, filed solely to enhance the value of a scientist’s resume and that the extensive expenditure of public funds spent in filing and maintaining patents was unviable.

Impact: Filings will reduce. Scientists will have to find alternative resources to file patent applications.

Read more in this link

 

Drug-abuse deterrent Guardian technology

Decision: Patents granted 9,549,899 (US); 2393487 (European); 2015200243 (Australian) owned by Egalet, a Pennsylvania-based company.

Reason: Novel Guardian Technology that encapsulates the drug in PEO polymer and a stabilizer makes it resistant to tampering. Methods for abusing prescription pharmaceutical compositions are varied and can include, for example, extraction, melting, volatilization, physical tampering (e.g., grinding, grating, crushing, etc.), or direct administration. Guardian protects against most.

Impact: Adoption of this technology by drug-manufacturers on formulations of major abused drugs.

Read more in this link

Win for generic Argentum on VIMPAT

Decision: Argentum, a generic manufacturer gets PTO to take UCB’s VIMPAT (antielpileptic/anticonvulsant) to Patent Trial and Appeal Board

Reason: The U.S. Patent Office granted Argentum Pharmaceuticals LLC’s petition for inter partes review and concluded that Argentum has established a “reasonable likelihood that it would prevail in showing that claims 1-13 of the U.S. Patent RE 38,551 are unpatentable.

Impact: Most likely UCB will loose the patent. A win for generic manufacturers who are questioning patents using post-grant review mechanisms.

Read more in this link

 

Myriad vs Esoterix (LabCorp) Tit for Tat DNA analysis patent fight

Decision: Pending. Esoterix is suing Myriad for patent infringement in the U.S. District Court for the Middle District of North Carolina, alleging that Myriad’s MyRisk Hereditary Cancer Test infringes the JHU patents that Esoterix licenses.

Reason: Myriad approached Patent Trial and Appeal Board for invalidating all four patents in question because they are obvious or anticipated because of prior research publications.

Impact: Unclear at the moment.

Read more in this link

 

iSPERSE Inhaled Drug Technology Patent

Decision: Patent EP 2410981 for iSPERSE owned by Pulmatrix.

Background: iSPERSE (inhaled Small Particles Easily Respirable and Emitted). A respirable dry powder comprising respirable dry particles that comprise a divalent metal cation salt; wherein the divalent metal cation salt provides divalent metal cation in an amount of about 5% or more by weight of the dry particle and wherein the respirable dry particles have a volume median geometric diameter (VMGD) of about 10 microns or less and a dispersibility ratio (1/4 bar) of less than about 2 as measured by laser diffraction (RODOS/HELOS system).

Impact: May replace aerosol and other blended dry powder formulations for inhalation. Pulmatrix applications pending in other patent offices as well.

Read more in this link

 

About the author:

Syam

Authored by Dr Syam Anand, PhD (Indian Institute of Science, IISc; Post-Doctoral research, University of Pittsburgh School of Medicine; Faculty, University of Pittsburgh School of Medicine, Founder and US Patent Agent, Mainline Intellectual Property LLC, Ardmore, Philadelphia USA). Syam has over 20 years experience in diverse areas of Science with domain knowledge in Life Sciences and Intellectual Property. Dr. Anand is also an inventor and budding entrepreneur. A rationalist, Dr. Anand enjoys science at all levels and advocates the use of scientific methods for answering all questions and solving all problems and make common people curious and interested in understanding their worlds.

https://www.linkedin.com/in/syamprasadanand

Featured Image source: Pixabay

 

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

 

 

Light Music for the Masses: A Story of LEDs

in SciWorld by

This blog was originally posted by Gaston Sendin (January 28, 2017) on neurokunst.com

Optics: fast and furious imaging

With optics coming of age and its widespread use in biomedical sciences, scientists invest substantial efforts in new imaging technologies. The aim is to reconcile versatility, performance and cost issues. Developments take place in the design of new molecules with expanded capabilities (e.g., increased resistance to photodamage, exquisite sensitivity to excitation frequency, chemical stability). But they also pursue the engineering of more flexible sensors and stimulators with improved performance (e.g. higher quantum efficiency detectors, higher signal-to-noise ratios and the choice of selectable wavelengths of excitation with narrower bandwidths).

Being able to quickly switch across different stimulation wavelengths while keeping them as narrow as possible is of great value for the experimenter. The optical properties of most materials largely depend on the wavelength that is used to study them. Working with “pure” light, as monochromatic as possible, is, therefore, a highly coveted aspiration that guides current efforts in optics.

The most popular type of optical setup in cellular neurobiology consists of a light source (usually a xenon lamp) coupled to a monochromator, a device that allows selecting a particular wavelength from the many available at the input. The output of the monochromator is coupled to the microscope and can, therefore, excite the biological sample lying under its objective. Although this design has been widely successful, to achieve a multi-band output and faster changes, some optical elements need to be brought on board, having an impact on the overall price. In a recent paper published in Nature Scientific Reports, Belušič and co-workers (1) found an elegant and inexpensive solution to circumvent this drawback and obtain multi-band stimulation at an extremely attractive price tag of 700€!

The LED synthesizer & how it works

The light source of this multi-spectral synthesizer, as they call it, is comprised of 20 LEDs of different colors, which are aligned in a row and forming an intrinsic multi-band light stimulator. The light coming from these LEDs is focused on a planar reflective diffraction grating. A grating is a flat optical component containing ridges at very precise intervals along its surface.According to the principle of diffraction established by Fresnel and Huygens, light hitting such a periodic structure is decomposed into several beams traveling in different directions. The wavelength of each light source and the spacing of the ridges on the grating set these trajectories. Diffraction of longer wavelengths (red) will be larger than shorter ones (violet). Therefore, using the grating, one can combine beams of different wavelengths.

LED synthesizer
                             The LED synthesizer in action!

The resulting composite beam then travels through a light guide equipped with a single aspheric lens. This lens minifies the diffracted “rainbow-type” pattern of colors produced by the grating and brings it into focus at its center. The combination of grating and light-guide fiber also had an unexpectedly beneficial consequence. The emerging light had significantly narrower spectral bands; the planar refractive grating not only combines several wavelengths into a single output beam but also cleans their spectra, narrowing their bandwidth.

What can we do with LEDs?

How about testing this gadget in a biological preparation? The authors used sharp electrodes to measure changes in the membrane voltage evoked by short pulses of monochromatic light, in photoreceptor cells from the blowfly’s eye. Stimuli were given with the LED synthesizer or with a classic photo stimulator. To map the photoreceptor’s response to light of different colors, they swept across a series of wavelengths, from 355 nm (ultraviolet) to 625 nm (red light) and were able to obtain a full spectral sensitivity curve in less than 2 seconds. These curves, constructed from the electrical responses to each wavelength presentation, were the same for both stimulation strategies.

As a proof of concept of its potential in biomedical imaging, they moved on to determine the absorption spectrum of oxyhemoglobin and deoxyhemoglobin species in a blood lysate. They presented a series of monochromatic light pulses spanning from 393 nm to 625 nm using either the LED synthesizer or a conventional spectrophotometer. A comparison of experimental results with tabulated data from the literature revealed that for measurements above 440 nm, both absorbance curves were nicely matching, indicating a similar performance for both optical devices.

Their next goal was to find out whether the LED synthesizer could as well discern between oxygenated and deoxygenated hemoglobin in a living tissue and therefore imaged blood vessels of the frog’s abdominal skin. Here the advantage is that oxyhemoglobin is enriched in the veins whereas arteries contain its deoxygenated counterpart. The results were very promising: they could identify spectral components containing enough optical information to discriminate between arteries and veins in the visual field, purely based on their absorption values.

Applications of the LED synthesizer

The LED synthesizer, therefore, represents a robust imaging device offering fast switchable control of the wavelength’s output and equalling to a large extent the performance of a monochromator-based setup, but at a considerably lower price. It can be assembled using inexpensive off-the-shelf equipment, namely cheaply available LEDs, a light guide, an aspheric lens and a planar reflective grating. The amount of undesired light (stray light) in the optical system is significantly reduced. LEDs also have a long operational life, a stable output and one can easily manipulate them and replace them if necessary, unlike the more cumbersome xenon lamps. When coupled to an ophthalmoscope, this imaging device is useful in clinical vision physiology (fundus examination, for instance) and more sophisticated applications in biomedical science (optogenetics, fluorescence microscopy).

Photodamage: Fluorescent molecules do not last forever. Upon repeated excitation, they undergo irreversible chemical changes after which they are no longer fluorescent. Photobleaching, as this process is also known, depends on the illumination level. Photobleaching is used in an optical imaging strategy called FRAP (fluorescence recovery after photobleaching), which is used to track the mobility of fluorescently labeled cellular proteins of interest. With this technique, we can selectively wipe out the fluorescence within a cell region and subsequently monitor its recovery as non-bleached fluorescently labeled proteins in the vicinity gradually start to repopulate the bleached area.

Quantum efficiency of a detector: the percent of incident photons that generate a signal. Not to be mixed with the quantum yield of a fluorescent molecule, which is a measure of its fluorescence efficiency, given by the fraction of all excited molecules that relax by fluorescence emission.

Signal-to-noise ratio: Electronic detectors are often compared by their signal-to-noise ratio, which is a measure of the variation of a signal that indicates the confidence in the measurement of its magnitude.

LED: Light emitting diodes. Resistors, capacitors, and inductors are linear circuit elements, meaning that a doubling of an applied signal (for instance, voltage) will lead to a doubling of the response (current). Diodes, on the contrary, are non-linear and let current flow in one direction, behaving as rectifiers. LEDs contain a semiconductor crystal coated with impurities that generate two regions: a negative n-region (charged with electrons), and a p-region (with positive charge carriers). If sufficient voltage is applied, electrons flow across the junction between both regions, releasing energy in the form of photons.

References

1) A fast multi-spectral light synthesizer based on LEDs and a diffraction grating.
Belušič G, Ilič M, Meglič A & Pirih P
Scientific Reports 6, Article number: 32012 (2016).
doi:10.1038/srep32012

2) Methods in Cellular Imaging, edited by Ammasi Periasamy, Oxford University Press, UK, 2001.

3) Imaging: A Laboratory Manual, edited by Rafael Yuste, Cold Spring Harbor Laboratory Press, US, 2011.

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Featured image source: Pixabay

Bad complements ?

in Reporting from the Lab by

Recently, we observed “Rare Disease day” to raise awareness of the rare diseases that afflict millions of people in the United States. While the definition of rare diseases varies in every country, in the United States a rare disease is one that affects less than 200,000 people at a given time. Scientists worldwide have made tremendous progress to identify and understand the clinical manifestations and pathogenesis of these diseases leading to several treatment options and saving many lives. In a recent article by Pandey et al in the journal Nature, scientists unraveled a critical role played by the body’s immune system in Gaucher disease, thereby prompting a potential treatment option.

Gaucher disease is an inherited disorder characterized by a mutation in the gene Gba1 that leads to a deficiency in the enzyme glucocerebrosidase.(GCase). This enzyme is present in the lysosome, the digestive system of the cell, that contains numerous enzymes necessary for the break down of complex molecules. GCAse, in particular, is required for the breakdown of a fatty acid compound, glucosylceramide (GC) into simpler components that can be recycled and utilized for other cellular processes. Consequently, a deficiency of this enzyme leads to the accumulation of GC within the lysosomes in the immune cells of the spleen, bone marrow and liver leading to chronic inflammation. The reason for this tissue inflammation remains elusive.

Enzyme replacement therapy (ERT) is effective in compensating for the enzyme deficiency associated with Gaucher disease. Genzyme’s Cerezyme (imiglucerase) was the first approved ERT treatment. Alternatively, substrate reduction therapy (SRT) prevents the formation of GC itself thereby reducing its accumulation. Two oral drugs, Actelion pharmaceutical’s Zavesca (miglustat ) and Genzyme’s Cerdelga (eliglustat) are commonly used for SRT. However, neither of them address the inflammation associated with the disease. The study by Pandey et al identifies a novel target that can help overcome some of the limitations of the current treatment and potentially benefit patients.

In a mouse model of Gaucher disease, Gba19V/-, Pandey et al found elevated levels of C5a in the immune cells of the spleen, liver and lung in these mice compared to normal mice. This was accompanied by an increased expression of C5aR1 in these cells. C5a is part of the complement immune system that plays an important role in inflammation and homeostasis. It is a cleavage product of C5 and is produced upon activation of macrophages and circulating monocytes, cells of the innate immune system that play a critical role in protecting the body by generating effective immune responses. C5a binds to the receptor C5aR1 on the surface of some innate immune cells that perpetuates the inflammatory response by activating another type of immune cells, namely T cells. Strikingly, double-deficient mice lacking GCase and the C5aR1 receptor (Gba19V/- C5aR1-/-) showed little to no GC accumulation and a significantly reduced inflammatory response with an improved survival. Another interesting feature of these double-deficient mice was the decreased expression of the enzyme glucosyl ceramide synthase (GCS), an enzyme that is required for the synthesis of GC. The treatment of Gba19V/- mice , with an antagonist compound that blocks C5aR (C5aRA) also resulted in decreased GC accumulation and reduced inflammation.

This study suggests that targeting  C5aR1 or C5 itself can potentially ameliorate inflammation and GC accumulation. There are two options available pharmaceutically to test this proposition in preclinical models. Alexion pharmaceuticals’ Soliris (eculizumab) is an anti-C5 monoclonal antibody that binds C5 and prevents its cleavage into C5a. It is currently approved for the treatment of a rare disorder, paroxysomal nocturnal hemoglobinuria. Another option is to target the C5a receptor (C5aR1) using antagonists such as Avacopan (CCX168) developed by Chemocentryx which is currently in clinical trials for the treatment of inflammatory disorders that affect the kidney.

Another interesting implication of these studies arises from the observation that Gaucher disease is closely associated with the neurodegenerative disorder, Parkinson’s disease (PD). Studies indicate that GCase and alpha- synuclein, the protein whose dysfunction is a major phenomenon in PD, have a reciprocal relationship and several ongoing investigations are focused on parsing apart this connection. This study published by Pandey et al opens up an area of investigation to determine the interplay between the complement system and inflammation in the brain that can perhaps explain the correlation between these diseases.

There are over 50 lysosomal storage disorders (LSDs) that are rare, inherited and commonly driven by enzyme deficiencies leading to unwanted accumulation of materials in the body. This study provides a promising therapeutic strategy not only for Gaucher disease but also for other LSDs associated with chronic inflammation.

Journal article :

Manoj K. Pandey et al, Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease, Nature (2017). DOI: 10.1038/nature21368

Additional newsfeed :

https://gaucherdiseasenews.com/2017/03/02/

study-says-

suppression-of-protein-

could-lead-to-new-gaucher-therapies/

http://www.alzforum.org/papers/complement-drives-

glucosylceramide-accumulation-and-tissue-inflammation-

gaucher-disease

https://www.sciencedaily.com/releases/

2017/02/

170222131459.htm

http://healthmedicinet.com/nature-study-suggests-new-therapy-

for-gaucher-disease/

Photo source : Stocktrek images

 Edited by Isha Verma

About the author 

Radhika completed her PhD from Cornell University and is currently a Postdoctoral fellow at the Brigham and Women’s Hospital. Her research interests have centered around oncology and neuroimmunology. Among other things, she is striving to effectively communicate scientific discoveries to the community.

 

 

The week that it was – 20th to 26th March, 2017

in ClubSciWri by
  • 894856_10151596530946703_1017119723_o.jpg?fit=2048%2C1379

CSG is now a platform with 6000+ members and CSG-Europe has started to bloom. Among the wide variety of information shared on the platform daily, I decided to bring you the opportunities to shape your future (of course, I know how you love to see them), help to deal with them and some refreshing foods for thought.

Time is ripe to attack the predatory science journals under the pretext of open access publishing, as researchers from Sussex carry out sting operation to expose 48 of them.

While Harvard Medical school scientists propose revising guidelines around genetic engineering, Nobel laureate Harold Varmus, Cornell Weill Medicine voices concerns around NIH budget cuts proposal.

Director of IISER Thiruvananthapuram, Prof. V. Ramakrishnan faces scrutiny for plagiarism; many academicians had objections to his appointment in the first place.

While CSIR lost enough of tax-payers money in filing non-revenue generating patents, researchers from IIT-Madras suggest possible solutions.

The market always loves and grooms the ones with exciting ideas –

  • Startup India brings free online extensive 4 weeks program for entrepreneurs to learn from the leading names in the country
  • Falling Walls lab, an initiative by German Centre for Research and Innovation, New York is looking forward to hear your research/ entrepreneurial idea to sponsor your meeting with other bright minds in Berlin, Germany
  • JoVE offers exciting prizes for filming equally exciting research work
  • And do not miss the opportunity to get connected with the pioneers in biotechnology in New York via the GRO BioPharma conference on 5th April

Illumina takes Next Generation Sequencing (NGS) techniques to fisheries; promises its help in increasing fishing yield.

Grab the openings-

With this mighty a list of openings, chances are high one of them interests you. Get started with the application then. Here are some tips on excelling your postdoc application, writing the perfect resume and cover letter. We don’t want to take chances here!

About the author:

Somdatta Karak works with Club SciWri as a project co ordinator and Corporate Liaison. She is a doctorate in neuroscience from Georg August University, Göttingen, Germany and has been a Teach for India fellow (2014-16). She loves putting her analytical skills to build newer and more sustainable solutions, enjoys traveling and communicating and takes every opportunity to expand her horizon.

You can reach her here.

 

 

Transitioning to Pharmaceutical Research: Face-to-Face with Mark Musters from Lead Pharma

in Face à Face by

Welcome mixers are great events at conferences. To introduce myself, I generally shorten my name not only for ease of communication but also to save 1-2 minutes in getting the pronunciation right. However, when I met Mark and introduced myself as Abhi he was quick to ask if I am Abhi or Abhinav. I realized my nametag gave that away. We happened to exchange several notes and by the end of the conference he was nice enough to agree to talk about his career transition to pharmaceutical research for ClubSciWri. It has been a pleasure to know about his work and career. – Abhinav Dey (AD)

Mark MUSTERS, PhD

Mark W.J.M. Musters (born 1980, The Netherlands) obtained his bachelor’s and master’s degree in Biomedical Engineering at Eindhoven University of Technology, followed by a PhD degree in computational systems biology at the same university in 2007. He continued his career at Wageningen University as a postdoctoral researcher by constructing detailed mathematical models of the central metabolism. In 2010, he started as a scientist at Lead Pharma, a small pharmaceutical company that develops innovative medicines to treat cancer and immune-related diseases. He is currently a project leader of an oncology and an immunology project.

AD: Can you briefly describe your role at Lead Pharma? What does a normal workday look like?

MM: Lead Pharma is a small pharmaceutical company (about 30 employees) that develops small molecular compounds to treat cancer and (auto-)immune diseases. I am a project leader of an immunology (atopic dermatitis) and oncology (metastatic melanoma) project. As a project leader, my main responsibility is that the project team develops potent and selective small molecular compound within a predefined time frame. A normal workday consists of structuring and coordinating all activities between the different groups (chemistry, molecular pharmacology, cellular pharmacology), informing team members and management about the progress, communicating with external parties, writing grant proposals and troubleshooting (if necessary). Besides being a project leader, I also analyze large -omics data sets to search for novel biomarkers and new targets that we could work on in the near future.

AD: What made you decide to move into industry rather than stay on the academic track?

MM: After completing my post-doc, I felt it was the right time to move to industry: I only worked for universities and research institutes and I was curious how working at a company would be. It turned out to be an excellent decision. The work at Lead Pharma is diverse and we collaborate in multidisciplinary teams towards a common goal. However, our fundamental research activities are limited compared to (top) academic groups and we do not publish our data either. That is certainly something to keep in mind.

AD: How did you prepare for your current interview? Which skills were essential apart from your scientific skills that helped you make the cut?

MM; I gathered information about the company (history, background of founders, mission, etc.), such that I could ask some questions during the interview as well. Personally, I think that I was hired because my personality matched very well with the company profile and I was honest in answering all questions during the interview. In addition, my pragmatic attitude and pathological optimism might have helped as well.

AD: How did your post-doc experience at prepare you for your position today?

MM: During my post-doc experience, I collaborated much more with “wet lab” experimentalists. Because I had a background in mathematical modeling, this trained me to communicate and understand biological research.

AD: Did you use any of the resources at your postdoctoral institution to prepare for your job hunt?

MM:Nope.

AD: How do you achieve work-life balance?

MM: Fortunately, our company offers its employees some flexibility and the management recognizes the importance of your personal life, which makes it easier to achieve a healthy work-life balance. This means that sometimes my workday is shorter, but a week later I work the whole weekend to finish an important presentation.

AD: Do you have any advice for postdocs considering careers in the biotech and pharmaceutical industry? What can they do to make themselves competitive?

MM: Prepare yourself! Read about how the pharmaceutical industry operates.  There are some good books available about drug development (and I don’t mean books like “Bad Pharma”). Ask yourself the questions: what would you like to do at a pharmaceutical company? And what unique expertise do you have that could help the company? That would be a good start.

 

 

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

Featured image source: Pixabay

From the Right Sense to that Perfect Shot: Anand Varma from National Geographic

in That Makes Sense/Theory of Creativity by
Honey Bee Larva in Plastic well plate

“But it seems to be less obvious somehow that to create anything at all in any field, and especially anything of outstanding worth requires nonconformity or a want of satisfaction with things as they are. The creative person — the nonconformist — may be in profound disagreement with the present way of things, or he may simply wish to add his views, to render a personal account of matters.” wrote Ben Shahn.

Working on my unconventional thesis on “creative folks in science communication” I happened to bump into Anand Varma, a science photographer by profession. If you love National Geographic, you might be able to locate his featured work there. Anand Varma shared his stories from his childhood and more with SciWri.

Curiosity and spirit of adventure dominated Anand’s childhood. He grew up in Atlanta, Georgia. Encouraged by his parents, he was found running into the creeks in the forest that extended beyond his backyard. His attention was captured by the leaping frogs and the trailing ants; he observed and tried to comprehend them as much as he could.

A bioluminescent mushroom from Brazilian forests.

This idea of observing the world around and exploring outdoors was, and remains, the motivation of his pursuits.

During his early teens, he was fascinated with different kinds of fish. His love for fish was so captivating that the idea of being an ‘ichthyologist’ enthralled him. Once he learned that one could be a scientist who observes fishes for a profession, it was the most obvious thing to do.

Soon after, he set out to be a biologist. One summer, he got the chance to assist and travel with a National Geographic photographer, David Liittschwager. That’s when it hit him that a photographer is as much as a scientist, exploring unknown, documenting it all through the eyes of an optical lens. Re-evaluation of his choices and aspirations led him to weigh his decision to be a science academician.  Academicians focus on a narrow question and spend a lifetime of work towards answering the same question in-depth. He realized he was someone with a short attention span and greater love for outdoors and exploration. A career in photography would allow him to stay outdoors, have fun exploring the world, meet interesting people, and understand a diverse set of problems that affect our world. He believes self-analysis and constant revaluation of interests and openness of mind and sight are the way to go forward. Anand believes that narrowing one’s goal to association with particular institute or a particular job may make one indifferent or blind to other good opportunities.

Like many who try to pursue unconventional routes, he grappled with uncertainty and fear of instability in trying to understand his choices and motivation, a process that took about four years. A creative, enriching pursuit was pitted against a comfortable certain path (a tenure track). It turned out that work kept pouringin and there was no time to take a break and reflect upon the choices. Academia became the fall back option and the walk to be a professional photographer continued.

Janthinobacterium growing in petridish.

He feels lucky to have been able to do what he is doing today, which is following his passion and making a meaningful living out of it. “It was so random,” he said, to have made a mark. While the career choice still has elements of uncertainty inherent to the nature of the job, he feels comfortable with his choice.

“Has the advice, ‘follow your passion’ held mettle or not?” I asked Anand. “While it is nice to ‘follow your passion,’ it is not a comprehensive advice,” he mused.  “One also has to find an audience for their love, find a way to connect with the audience. If one wishes to pursue their passion as a career, one has to evaluate the worthiness of their passion for an audience, however big or narrow.” He believes that your passion has to produce something that other people value.

Another thing that comes as part and parcel of this advice is that one must be prepared to live with anxiety and risk. Taking risks and plunging into an unknown experience and surviving them is how one learns to live with the fear. One does not always know what the outcome will be. On the lines of what Maria Popova said, one must regularly update their goals and choice to be on the path. That would mean walking into unchartered territories again and again and having to live with uncertainty and anxiety.

A prepared mind and open eyes are a must for one to be able to evaluate opportunities. He advised that one must not pin goals to a specific job or organization, but rather that goals should be about what one wants to do more generally. He knew that he wanted to explore nature and be outdoors, it was not his goal to work for the National Geographic. This allows one to be open to a wider range of ‘compatible’ opportunities and less dependent of the whims of a specific company or institute. The bigger picture also allows one to identify the ways to connect with an audience.

Close up of female Coppery-bellied Puffleg hummingbird.

He has now been a photographer for a decade. As someone who believes in the evolution of choices and goals, he now wants to improve his storytelling skills and collaborate with talented storytellers in other fields. He aims to find more innovative ways to answer the question, ‘how do you get people to connect with nature?’

As part of understanding what he wants to learn, he and Prasenjeet Yadav conducted a science photography workshop at NCBS, Bangalore. From the questions participants asked, he hopes to identify central ideas about, ‘how does one tell a story?’ The biggest factor, he believes, lies in understanding the audience to know what their interests are; what they already know and how what you have to share will add novelty or value to them.

If one looks at the body of work that Anand has created, novelty is certainly one of his motivations. He seems to have a signature style where he strives to create a novel and striking way to portray subjects that have been photographed previously. I asked him about his inspirations and influences in the making of what I think of as ‘the Anand Varma style’. He said, “It is a personal call most of the time. I took me a long time to make photographs that I was satisfied with.” This is a reminder of Ira Glass’s observation that great artists start with a good sense of taste, and they succeed when they figure out how to produce work that matches the standards they set for themselves.

 

'Mind controller' horse hair worm comes out of house cricket
‘Mind controller’ horse hair worm comes out of house cricket. 

Talking about influences, he mentioned two contrasting themes. His initial training was with National Geographic photographer David Liittschwager. David appreciated the power of simplicity where the subject is drawn far away from its context, and one can enjoy all the details of the subject up to the stray hair on its face. Another influence was from Japanese animation where each frame has so much visual information that it is difficult to blink one’s eyes without missing out on magnificent details.

He strives to find a balance between maintaining simplicity while cramming in visual information to hook the readers. According to him, a good image is one where you would not want to take your eyes off it. The balance between mystery and familiarity is what makes an image striking.

The wisdom he shared with me speaks to the volume of experience he has gained, despite being a relatively young artist. “A wise person is an experienced person. Practical wisdom is a craft and craftsmen are trained by having the right experiences. ‘People learn how to be brave,’ said Aristotle, ‘by doing brave things.’ So, too, with honesty, justice, loyalty, caring, listening, and counseling”, wrote Barry Schwartz and Kenneth Sharpe in their book Practical Wisdom: The Right Way to Do the Right Thing. I hope to seek newer experiences actively and plunge right in. How about you?

 

About the author

Ipsa Jain is Ph.D. student at IISc. Wants to gather and spread interestingness. Prefers drawing and painting over writing. Posts on Facebook and Instagram as Ipsawonders.

 

 

 

Walk from academia to photography: Prasenjeet Yadav

in That Makes Sense/Theory of Creativity by

“To be, or not to be: that is the question: Whether ’tis nobler in the mind to suffer the slings and arrows of outrageous fortune, or to take arms against a sea of troubles… And indeed, that IS the question: whether to float with the tide, or to swim for a goal. It is a choice we must all make consciously or unconsciously at one time in our lives. So few people understand this! Think of any decision you’ve ever made which had a bearing on your future: I may be wrong, but I don’t see how it could have been anything but a choice however indirect — between the two things I’ve mentioned: the floating or the swimming.” wrote Hunter S. Thompson in letter to his friend Hume Logan.

During his journey, Prasenjeet Yadav has shuffled his choices, from what may seem being a ‘floater’ to a ‘swimmer’.  He started out as a science student from a small city (Nagpur) who worked his way up to get a research position at National Centre for Biological Sciences (NCBS), as well as improve his linguistic skills in English. While pursuing research on Tiger genetics as a research fellow, he made the choice of leaving academia and to take up science photography professionally. In this interview he speaks to Club SciWri about his story.

I.J. When and how did you fall in love with science?

P.Y. I was always curious about the world around me and it was the result of my curiosity that made me start caring about science and nature. I grew up in Central India, on my father’s farm near Nagpur surrounded by jungle. ‘How?s’ bothered me as much as ‘what?s’ did. I wanted to understand the behavior of animals, stripes of tigers, color of the snakes, and calls of the birds I would see around me. The folk tales I heard while growing up were laced with wild jungle characters and I would wonder why they behave the way they do.  I often got anecdotal responses from the elders in the village, which did not sound reasonable even then.Science was the lens through which the behaviors made sense. Back in school it was the only subject I studied for,and managed to pass (laughs).

Farm in Nagpur where Prasenjeet grew up

I.J. When was your first brush with the camera?

P.Y. (long story) I was the guy in the school class who did not care about cricket, not a very common place thing among children of my generation in India. I was met with jibes and taunts when I would abruptly talk about the leopard I saw.  I knew then pictures would be the proof of my experiences. I anyways liked the idea of taking a moment from time and give it to infinity. It was profound, so fascinating. My father had some interest in photography. He gifted me a ‘hot shot camera’. It had one roll, one view finder, a lens and you click. I actually had to earn the roll and the allowance to develop by cleaning my dad’s vehicles every morning at 6 AM. I spent my time looking at the world through the viewfinder of that hot shot camera trying to get that one perfect shot. Things changed when I bought my first SLR camera, after coming to Bangalore. After setting up thousands of PCR reactions, I would spend my evening capturing ants and frogs and snakes at the herbarium in the campus.

Praying Mantis

I.J. When did you decide to make the call of going over to photography completely?

P.Y. It was during the time, a year almost, that I spent at the herbarium that made me realize my interest and potential in photography. Honestly, I knew I wasn’t an academic genius, but I was hard-working. I felt that despite getting my work published in decent journals,I was not sure if that is what I wanted to do any longer. However, during my time as a researcher, I spent a lot of my time talking to my engineer friends who only perceived me as a tiger poop collector. I took some efforts to explain them my research, and I realized I enjoy communicating science. It keeps my curiosity alive. During the process of my research, at some point it went into too many details where I felt my curiosity slipping away. While I understand the importance of intricate details in research, I do not feel that I could do this for long.

Steam glory on a leaf

I.J. You often say, “I am made of my failures”. What are the failures you refer to?

P.Y. I think what you define and perceive as a failure really depends on your perspective. At a time, flunking in chemistry exam was a failure. Looking back at it now, it’s just plain hilarious. There was a time in my academic career that I started feeling that I was not satisfied enough. I was failing my own expectations for a good academic career. I realized I was not doing well and there seemed no point in continuing this. I was in a matrix- of science, conservation, and photography and science communication. I was standing at one end and hoping all of it funnels towards me. Well, that was not happening and I felt, I was failing.  I realized I should just change my position in this matrix. Looking back, it was not a very conscious decision, but rather I followed my intuition. I believed if I do what I like; things will eventually fall into place. What was once my ‘failure’, is now my strength. I understand better the science of the subjects that I photograph. I understand the jargons in the community and can make sense of things. The ‘failures’ have set a foundation for leaps in my current choice of career.

I.J. How did people perceive after you ‘quit’?

P.Y. After I quit, I called up my mother who is quite cool, and told her about my decision. She said, ‘Okay, padh-likhleta to acha lagta’ (roughly translates to: Okay, if you had gone on to study, it would have felt better). But gratefully, my parents did not object to my choice. I guess my financial independence also helped. However, I felt like a failure because I quit my research within three years while others had put three decades into their research. I couldn’t help myself out of this. And I feel my own opinions about myself were being reflected in people’s perception of me. And I took their perception seriously; it was a reality check for me to evaluate my situation better.

I.J. What have you been upto since you ‘quit’?

P.Y. I like to observe and observe and observe. I like to identify processes, look for some patterns and tell a story. That’s how I got into science in the first place, seeking a good medium to look for meaningful patterns. I have been experimenting with the camera. I got my first gig by chance. Me and my friend, we were dog-sitting for an NCBS professor while he was away. During that time, a BBC filmmaker KalyanVarma landed up at the house looking for the professor. Instead, they ended up talking to me. They were planning to make a movie on monsoon. I suggested the story of migration by nomadic Dhangars tribe and their relationship with pack of wolves that follow them. Filmmakers got excited by the idea and later I ended up working with them for six months in Central India for the story. After that, I documented a project for NCBS, Govt. of Sikkim and Ashoka Trust for Research in Ecology and the Environment that was funded by Department of Biotechnology. I went to Sikkim and documented the work Sikkim students were doing across various fields on diversity and ecosystem of the state. I developed it into a photo story that was appreciated by funding agencies and the researchers alike. After that, a lot of people who in my perception, thought of me as a failure came around and appreciated my work. It felt nice and made me realize that the work like this has a lot of value.

A sikkim researcher measuring forest cover

Slowly one thing led to another, and I published with many major magazines and newspaper house In India. I realized that the stories I did were not just specific to Indian audience and had international value. They were stories on conservation, climate change, sustainable energy etc. Then I looked for opportunities and found National Geographic Young Explorer grant. I applied for it and actually got it. That is the time when I felt, did National Geographic just approve of what I have been doing! Since then I have worked on various projects with them. They have helped my growth tremendously by sending me to photojournalism workshops, recommending me for several international film and photo festivals etc. I call myself freelance photographer but in last three years, I have freelanced only with National Geographic (chuckles).

Frog mating

I.J. What is your opinion of a good photograph?

P.Y. I believe that a good photographer is not the one who takes a good picture of snow leopard. Snow leopard is exquisite; any picture of it will be worth. A good photographer is someone who can make stunning, novel and an interesting picture of the most common subjects such as ants. It’s the story and perspective that matters more than the equipment.

Scorpion (clicked under UV light)

In conclusion, I would quote Hunter again, “I’m not trying to send you out ’on the road’ in search of Valhalla, but merely pointing out that it is not necessary to accept the choices handed down to you by life as you know it. There is more to it than that — no one HAS to do something he doesn’t want to do for the rest of his life.”

About the Author

Ipsa Jain is Ph.D. student at IISc. Wants to gather and spread interestingness. Prefers drawing and painting over writing. Posts on Facebook and Instagram as Ipsawonders.

Filing taxes in US for non-resident aliens

in That Makes Sense by

According US tax return policy, every citizen filing tax returns as single gets a standard deduction of $6,300 and a personal exemption of $4,000. Standard deduction is a non-itemized fixed amount that is deducted from the net income. Personal exemption is an amount that a taxpayer can claim as tax deduction against personal income. These values reduce the taxable amount for all the taxpayers. India and USA shares a tax treaty that makes it easier for Indians to file taxes in US. According to this treaty, Indians gets a standard deduction of $10,300 ($6,300+$4,00). This makes tax return process similar to US citizens for Indians. Similar tax treaties for different countries are also available. However, process for Chinese citizens is bit different and requires complex tax return calculations. It is very easy is get confused when it comes to remembering form names for tax purposes. I learnt it in a harder way, so I’ll try to simply things for people.

Forms to know:

 

  1. W4: W4 is an IRS form provided by your employer to declare the amount that will be withheld from employee’s pay for federal income tax (A snapshot of W4 is shown adjacent to text). More you withheld more you get back from tax returns. For a F1 student, graduate school or payroll will help you in filling W4. After filling the form, ask the officer about the amount that will be withheld. It is important to see that you are left with sufficient money for monthly expenditure. 
  2. W2: W2 is a form that is provided by your employer at the start of the year. A sample copy is pasted along with the text. This form declares your wages and the tax withheld by IRS. It generally comes as a 4-copies (there are other versions of it, but none of them concerns us). A copy has to be sent to IRS for federal tax return, another copy goes to state and/or city tax department. Finally, the last copy is for employee’s record. Each copy of W2 will mention where it has to be sent (see the black box at the bottom left corner). W2 is the only way of your communication with IRS. Hence, it is necessary that all the information on the W2 form be verified before filing tax returns. Employer’s and employee’s name and address (blue arrows) and employee’s SSN (green arrow) needs to be verified. The green box on the right shows all your income from a particular employer (you will receive multiple W2 if have more than 1 employer) while blue box highlights the amount withheld by IRS.
  3. 1040-NR/1040NR-EZ:US tax return form is popularly known as 1040. Being a non-resident alien your tax return form will bear a NR designation making it 1040-NR. To further simplify things, an easier version of the same form is available known as 1040-NR EZ (1040-NR easy). However, you will have to make sure which form is the best for you. Depending on your situation, 1040-NR EZ may not be applicable for you. To put it in simple terms, if you are a student or post-doctoral scholar who is filing tax as single (no dependents) you can use 1040-NR EZ. Following links will be helpful in deciding which form to use.

 

How to file your taxes:

 

  1. Many universities provide access codes to certain sites for filing tax return for free. However, this is not universal. Some universities or institutions have no such programs. In that case, one can go to professional tax filing institutions such as H&R block. They will charge you around $10-$50. International students can also use websites such as sprintax (sprintax.com). This is an international student version of turbotax (www.turbotax.com). Turbo tax provides form 1040 and 1040-EZ, which are applicable only for green card holders and US citizens. The best option, according to me, is to look for VITA (Voluntary Income Tax Assistance) centers. They file tax returns for free for people earning less than $54,000 p.a. IRS website provides details about VITA centers and also have a tool to locate VITA centers near you. Some catholic charities also help to prepare free tax returns (This is mainly for NY). Following is the link for VITA center locator. https://irs.treasury.gov/freetaxprep/
  1. Make sure to ask the VITA center if they can file tax for international students. It is possible that not all VITA centers have authorized personnel for international students. If they cannot file your tax, it is likely that they will provide you with the details for nearest VITA centers for international students. You can also call 2-1-1 to fix appointment with VITA centers. ALWAYS MAKE SURE TO ASK WHETHER THEY CAN FILE TAX RETURN FOR INTERNATIONAL STUDENTS.
  2. This is applicable exclusively for 1st year graduate students: A new graduate student is likely to make less than $14,000 in their first year. Filing a 1040/1040-EZ instead of 1040-NR/1040-NR-EZ will make them eligible for “Earned income credit”. This results in extra $400-$500 in their tax return, which appears tempting. You will get suggestions from your friends as to go forward with it, as IRS will not grant you that money if you are not eligible. Since, they are using 1040 instead of its NR version, IRS will consider them as US citizens, and it is highly likely that they will receive that amount. Earned income credit is exclusively for US citizens, and if you are getting that option during tax return then you are doing something wrong. If you are thinking of staying in US and applying for green card, then background check at that time will bring this on top and you will not only have to return the money but also pay interest on it.
  3. This is applicable for everyone: If you have filed 1040 instead of its NR version, then don’t panic. Remember the India-US tax treaty I talked about in the first paragraph. This treaty has saved you. You will just have to file an amendment and that process will transfer your information for that tax year from 1040 to 1040-NR. As our standard deductions are same as US citizens, your tax was still calculated accurately and you owe nothing to IRS. Amendments can be filed anytime of the year.
  4. For J1 visa holders, a 2-year tax exemption treaty is present. There is point to remember for this situation. For tax purposes, US count even a 1-day stay in tax year as 1-year stay. For instance, if you arrived in US on 30th December 2016 you should be eligible for tax benefits for year 2017 and 2018. But according to IRS, you were in US in 2016. This will make a change in calculation making 2016 and 2017 as your two-tax benefit year. So, if possible, try to extend the start or change your trip plans by a week.
  5. Even if you take help from any VITA officers, H&R block and websites, you and only you will be held responsible for any discrepancies in the form. MAKE SURE TO VERIFY ALL THE INFORMATION BEFORE SIGNING THE DOCUMENTS.

 

 

Abhinit Nagar

Graduate student

Department of Immunology and Microbial diseases

Albany Medical College, Albany, NY.

Image source: Pixabay

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

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