Job opening in Dr. Reddy’s

Designation : Research Associate – Cell line Development

Job Description :

1. Molecular biology: Cloning to prepare constructs and preparation of transfection grade DNA for vector constructs to enable cell line development.                                         

2. Participate in experiment design, follow instructions and perform experiments, keep accurate records, generate and collate data for analysis and discussion to make meaningful conclusions in order to establish high expressing stable cell lines effectively by:

a) Establishing stable pools with different constructs.
b) Evaluation and selection of top pools based on fed-batch study.
c) Semi-solid plating of top pools for clone screening and selection.
d) Evaluation of top clones for productivity in a fed-batch study using scale down models for cell culture and shale flasks.
e) Establishing research cell banks (RCB’s) 
f) Determining preliminary generational stability of the top clones.
g) Selection of top clones based on productivity, stability and quality.
h) Establishing medium sized RCB’s for top clones to enable development and campaign studies in cell line and process development space.                                                                

3. Learn techniques, execute experiments with expected quality as per the instructions and defined procedures and maintain precise records of data to enable troubleshooting at any point.                                                                                                           

4. Actively participate in data analysis and prepare presentations for discussion in CLD department meetings.                                                                                                                   

5. Remain current in the field by review of relevant scientific literature and attendance at appropriate scientific seminars and conferences.

Department : Biologics

Open Positions : 2

Skills Required : Molecular biology, cell culture, cell line developement

Location : Bachupally, Hyderabad, Telangana, India

Education/Qualification : M.Sc – Technology

Years Of Exp : 3 to 5 Years

Apply here : shorturl.at/fsuIV

Job opening in Sun Pharma

Opportunity in R&D Biotech – Sun Pharma, Baroda Executive / Sr Exe – Protein Characterization
JD :
1. Analytical method development for recombinant proteins characterization. 2. Validating test methods used in product characterization
& bio-similarity assessment.
3. Independently design and perform analysis, including but not limited to, HPLC/UPLC, CE, Mass Spectrometry, ELISA, cell-based assay and others. Interpret results and write
report with sound rational.
Send in your updated cv to Rosemary.varghese@sunpharma.com

Impact of mAb Aggregation on its Biological Activity

Dr. Rozaleen Dash’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Dr. Dash completed her PhD in Biochemistry from All India Institute of Medical Sciences, New Delhi then, she joined as Scientist- B at Maulana Azad Medical College, New Delhi. Currently, she is doing Post-Doc as a ICMR-RA fellow in the Professor Anurag S Rathore Lab, Department of Chemical Engineering, Indian Institute of Technology Delhi, India. She has expertise in Functional Characterization of biotherapeutics, Comparability of Biosimilars and Drug immunogenicity. Here, she talks about her co-first author research article titled “Impact of mAb Aggregation on Its Biological Activity: Rituximab as a Case Study” published in the Journal of Pharmaceutical Sciences (2020).

How would you explain your papers’ key results to the non-scientific community?

Monoclonal antibody products (mAbs) are prone to molecular instabilities like aggregation, fragmentation, oxidation, and reduction. Aggregation phenomena is a common issue for technological advancement in mAbs production which can induce adverse immune responses in patients that may affect safety and efficacy. The factors that influence the mAbs aggregation, including physical, mechanical, and chemical stresses. These stresses may form during manufacturing, storage, filling, formulation development, and shipping. Growing data suggested that mAbs aggregation can enhance immunogenicity, yet underlying mechanisms are not fully understood. Further understanding mAbs aggregation phenomena helps develop robust analytical techniques for monitoring the aggregational level and precise nature of mAbs aggregation. Our recent paper includes the physical characterization of protein aggregates generated by different stress treatments by a host of analytical techniques like DLS (Dynamic light scattering), SE-HPLC (Size-exclusion chromatography), TEM (Transmission electron microscopy), and Fluorescence spectroscopy. Apart from physicochemical characterization, these aggregates were also characterized to evaluate their impact on the biological activity of mAb molecule by a wide variety of tools such as SPR (Surface Plasmon Resonance), FACS (Fluorescence-activated cell sorting), ADCC (Antibody-dependent cell cytotoxicity) and CDC (Complement-dependent cytotoxicity). We demonstrate the extent of aggregation, the nature of aggregates, and the impact of aggregates on biological activity all depend on the source of aggregate formation. This study illustrates the ability of different analytical tools in characterizing aggregate species as well as in determining their impact on biological activity. The results affirm that understanding the mechanism of aggregation is critical for achieving consistent product quality.

Figure 1: The workflow of mAb aggregates with biological potency resulting in immunogenicity. Our studies show extreme pH (pH 3.5 and pH 11.0), stirring (1 d and 3 d stir) and oxidation via CuSO4 have the most impact on aggregate formation and the biological potency of the therapeutics.

“This study illustrates the ability of different analytical tools in characterizing aggregate species as well as in determining their impact on biological activity.”

What are the possible consequences of these findings for your research area?

There is a possibility that the impact of aggregates on the bioassays could be analytical artifacts, suggesting hyperactivity. Without a doubt, further studies are required to acquire a deeper and more accurate understanding of aggregation phenomena. These could include in vivo testing of the immunogenic potential of these mAb aggregates formed under the extreme pH, stirring, and oxidizing stress conditions. However, we hope that the results presented in this study would be of significance to those in academia and industry working on protein formulation and stability.

What was the exciting moment (eureka moment) during your research?

Our results related to physicochemical and biological characterization tools for mAb aggregates were highly rewarding, and the SPR study was relatively more challenging. We found no or minimal binding affinity with the receptor in SPR studies. The KD value increased with percentage aggregates and was very clear from the SPR sensorgrams. This moment proved to be a “Eureka” moment as executing SPR studies successfully for challenging mAb aggregates.

What do you hope to do next?

Multi-domain monoclonal antibodies are far more complex than small molecule drugs with various intrinsic heterogeneities that are typically well characterized for identity and bioactivity. The critical quality attributes (CQAs) of a mAbs, include product-related variants i.e., aggregation, charge variant and glycosylation. Keeping this in view, my next proposed work intended to understand the precise molecular mechanism underlying the structure-function relationship during the aggregation process.

Where do you seek scientific inspiration?

Science is a way of life, a zestful drive that allows researchers to fuel their dreams into reality. Since childhood, I have been motivated by a fascination for science and a burning desire for enquiry. I gained my scientific inspiration from my mentors Prof. Nibhriti Das (PhD guide) and Prof. Anurag S Rathore (Postdoc guide). They are amazing persons I ever met, and they are my continuous inspirational source in my research career.

How do you intend to help Indian science improve?

I believe my passion, expertise, knowledge, and skills will help develop and further advance the Indian scientific vision in the domains of affordable biotherapeutics and drug discovery. I hope that my research reaches out to a broader audience and is accessible to all.

Reference

Bansal R#, Dash R#, and Rathore AS. Impact of mAb Aggregation on its Biological Activity: Rituximab as a Case Study”. J Pharm Sci. 2020; 109(9): 2684- 2698. doi.org/10.1016/j.xphs.2020.05.015. #equal contribution.

Prof. Anurag S Rathore’s lab webpage: http://biotechcmz.com and https://cbt.iitd.ac.in

Edited by: Govinda Raju Yedida (Volunteer, Bio Patrika)

Withaferin A as a potent regulator of hepatocellular carcinoma

Varsha D. Shiragannavar’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews.

Varsha is currently a second year Ph.D. student working in the lab of Dr. Prasanna K. Santhekadur at Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS AHER, Mysuru. Her doctoral studies is primarily focused on investigating the role of RNA-induced silencing complex and associated proteins in the progression of non-alcoholic fatty liver disease and hepatocellular carcinoma. She is trying to understand the molecular/cellular process on how RISC complex genes and protein are regulated when treated with many dietary natural products. Here, Varsha talks about her work titled “Withaferin A Acts as a Novel Regulator of Liver X Receptor-a in HCC” published as first author in Front Oncol 2021.

How would you explain your paper’s key results to the non-scientific community?

Over the past two decades rapid changes in the lifestyle around the globe including India having a significant impact on liver diseases such as Nonalcoholic fatty liver disease (NAFLD), and associated Hepatocellular Carcinoma (HCC). Recent reports from Zydus Cadila pharmaceutical company suggested that Indians around 400 million are suffering from Fatty liver. Currently, there are one or two drugs available in the market to treat NAFLD and HCC. Therefore, this study has an urgent need for Pharmaceutical Industries and clinical research.

The famous quote by the Greek physician Hippocrates states that “Let food be your medicine and let medicine be your food” has stood the test of time. Natural dietary compounds are gaining increasing popularity in recent years as pharmaceutical drugs due to their pleiotropic effects and multifaceted beneficial properties with less or no side effects. Ashwagandha/ Withania somnifera is not new to Indians and is one of the most important plants profoundly used in ancient Ayurvedic medicine. This plant used as a medicine for the past 3,000 years, and this products, including, roots, leaves, berries and stem have been used as rejuvenator drink/tonic, anti-oxidant and paste to treat wounds. Also, used to treat stress, anxiety, aging, autoimmune diseases, inflammation, and many other diseases. Withaferin A is a steroidal lactone isolated from Withania somnifera plants, belongs to withanolide family of compounds. Withaferin A is one among more than 50 chemicals identified in Withania somnifera extracts which have medicinal properties.

Figure 1. Schematic representation of Withaferin A-mediated regulation of LXR-α and NFҡB signaling in HCC.

In this study, we demonstrated that Withaferin A, a natural compound has inhibitory effects on aggressive behaviour of HCC cells and how they are activating nuclear receptor LXR- α. Interestingly, withaferin A decelerates various cancer hallmarks such as proliferation, migration, and invasion. Also, downregulate anchorage-independent cell growth ability, LXR-α mediated NF-ҡB activation.

Hence, we think that translating the use of Withaferin A for the treatment of HCC in humans holds great promise near future.

“Our work presents a possible novel mechanistic model that Withaferin A may negatively regulate NF-kB transcription factor via activating LXR- α”

What are the possible consequences of these findings for your research area?

The ligand molecule withaferin A affects LXR- α was studied, and its role in inhibiting HCC was promising. However, molecular interactions of Withaferin A with various genes or transcription factors were not known. Our work presents a possible novel mechanistic model that Withaferin A may negatively regulate NF-kB transcription factor via activating LXR- α (Figure 1). Withaferin A acts similarly to the already approved drug for NAFLD, Saroglitazar an Indian origin drug. Saroglitazar widely described acts on PPARα/γ whereas, withaferin A acts on another nuclear factor called LXR-α. Reports suggested that LXR-α activation potentiates sorafenib sensitivity in HCC cells.  Our finding shows that withaferin A activates LXR-α, therefore Withaferin A has all the potential to sensitize HCC cells in presence of sorafenib. Withaferin A also has the potential to kill HCC cells via activating LXR-α and inhibiting NF-kB.

What was the exciting moment (eureka moment) during your research?

Eureka moment for me was when we found out that Withaferin A induces LXR- α target genes. On the other hand, when we found Withaferin A inhibits NF-kB target genes via LXR-α. These two findings were eureka moments for me!

What do you hope to do next?

We now know that Withaferin A has decelerated many hallmarks of cancer through this study. Further, we will explore the possible role of RNA-induced silencing complex in non-alcoholic fatty liver disease, and hepatocellular carcinoma development and progression. Later, we intended to investigate molecular interaction using dietary natural compounds on inflammatory signalling pathways, mRNA regulation, protein expression, translational modification in in vitro and in vivo. Based on our results from in vivo diet induced animal model of obesity and NAFLD and HCC xenograft studies, we will be planning to go further for phase1 clinical trials.

Where do you seek scientific inspiration?

I have always been fascinated by how life exists on earth. This was the reason why I chose biology as the main subject during my education. After my masters, I grabbed the opportunity to do research under the guidance of Dr. Prasanna K. Santhekadur at JSS Medical College, JSS AHSR, Mysuru. I have always been inspired by him for his motivational and scientific talks and discussions to actively pursue new ideas and implement them. He has always taught us the importance of “Positive Imaging in life as well as in academic research”. This drives me to work harder and smarter with great values and positive thinking. We have good lab culture and healthy competition to successfully complete my doctoral research.

How do you intend to help Indian science improve?

Today’s children are tomorrow’s future of India. Enlightening the young minds with the current trends in science and encouraging them to choose the field is essential. We are planning to conduct interactive sessions (Talk to a Scientist program) with school children introducing them to the whole new world of science. As a researcher, I would like to contribute to the mankind by developing novel drugs to treat NAFLD and liver cancer.

Reference

Shiragannavar VD, Gowda NGS, Kumar DP, Mirshahi F and Santhekadur PK (2021) Withaferin A Acts as a Novel Regulator of Liver X Receptor-a in HCC. Front. Oncol. 10:628506.

Email ID: varsha.ds08@gmail.com

Edited by: Govinda Raju Yedida (Volunteer, Bio Patrika)

Women in science: I am a woman, a wife, a mother, and a scientist!

About


Dr. Manveen K Sethi serves as Instructor of Biochemistry at the Boston University School of Medicine, USA. She did her Ph.D. at Macquarie University (MQ), Australia, under the primary supervision of Dr. Morten Thaysen-Andersen,where she utilized mass spectrometry proteomics and glycomics analysis to understand underlying molecular mechanisms in colorectal cancer . After her Ph.D., she joined Boston University School of Medicine (BUSM), USA, as a postdoctoral associate under Prof. Joseph Zaia, where she is currently employed in a research faculty-track position of Instructor. Her research work involves identifying and characterizing biomolecules such as proteins and glycans using mass spectrometry techniques and utilizing this information to understand biomolecular deregulation in human diseases, such as cancer and Alzheimer’s disease. Recently, she received a Bright Focus Foundation fellowship award to investigate extracellular matrix changes in Alzheimer’s disease.


I was born and raised in India, a highly diverse and multicultural country, yet one where patriarchy holds power and women are presumed weaker. I grew up in a middle-class family and was the middle child with an elder sister and a younger brother. Even though we were raised with equal opportunities with respect to education and well-being, I have seen the disparity in other households where a male was allowed opportunities not open to a female. Thus, growing up, I always wanted to prove that females are no less than males; they can go beyond the household, achieve and fulfill their dreams, and excel professionally. I believe my unique personal circumstances and surroundings made me a hard worker who overcomes challenging problems with creativity and perseverance. Unfortunately, even science is not immune to such disparities and inequalities, with only one-third of women researchers globally. Thus, I realized at the very beginning that being a female in the world of science is not easy. I have to work hard to fit in with the challenging science world. On one side, I have to tackle my job. On another side, I have to tackle my personal life as a wife and a mother but creating a balance in scientific and personal life is essential to embrace life both as a scientist and a woman with dedication and diligence.

I have lived a cosmopolitan life, traveling and living in different countries and attending conferences worldwide. I have studied in India and Australia and worked in India, the United Kingdom, and the United States. Thus, I have been exposed to diverse peoples, cultures, and traditions. I believe the cross-culture experience helped my personality development and played a significant role in my personal and professional life.

I have always been inquisitive. When I was a child, I questioned the smallest day-to-day things from “why a firefly light” to “why onion made us cry.” With a childhood science interest, I eventually pursued a bachelor in science (honors.) in chemistry, followed by a master in science chemistry degree from Delhi University, India.

Ph.D. graduation picture, Sydney, Australia (2015).

After completing my master’s degree with an academic excellence award, I attained UKIERI (UK-India education research initiative) fellowship to work as a trainee research chemist at GlaxoSmithKline (GSK), United Kingdom. This was an exceptional opportunity that enhanced my professional and personal skills. I also received a GSK reward and recognition for my work. After this, I briefly worked as a research chemist in India before attaining International Macquarie Research Scholarship (IMQRES) to pursue a Ph.D. degree at Macquarie University, Australia, with Dr. Morten Thaysen-Andersen, who is an internationally recognized researcher in the field of glycomics and glycoproteomics. Early in my career, I have had a desire to study human health and disease. During my Ph.D., I became devoted to making an impact in the field of cancer, evident by my scientific contributions to the field, including my frequently cited CRC paper (Sethi MK et al., J Proteome Res, 2014, IF 4.3, 85 citations, Sethi MK et al., J proteomics, 2015, IF 3.5,53 citations). My article Sethi et al., Glycobiology, 25(10):1064, 2015 (IF 4.0, 54 citations), due to its innovation and novelty, was selected as a front cover on all 12 journal issues throughout 2016. After my Ph.D., I was offered a postdoctoral research fellowship at Boston University School of Medicine (BUSM), USA, under Prof. Joseph Zaia, an internationally acclaimed leader in mass spectrometry (MS) and Glycoscience. Currently, I work at Boston University as the Instructor of Biochemistry, a research faculty track at BU, and my next position will be Assistant Research Professor. At BU, I have learned (and further developed) MS-based techniques of proteoglycans (PGs) and glycosaminoglycans (GAGs) (Sethi MK et al., Mol Omics, 2020; Raghunathan R, Sethi MK, et al., Methods X, 2019) and applied these techniques to disease models in neurodegeneration including Schizophrenia and Alzheimer’s disease (AD) as evidenced by my recent publications (Muraoka S*, DeLeo AM, Sethi MK* (*co-first author) Alzheimer’s Dement. 2020; Chen J, Kawamura T, Sethi MK, et al., Sci Rep, 2017).

I have been fortunate to provide my service to the scientific community as an Instrument Manager for Thermo QExactive HF mass spectrometer at Center for Biomedical Mass Spectrometry, Boston University, President of Boston Glycobiology Discussion Group (BGDG), and as a reviewer for many renowned scientific journals. I have widely disseminated my research at prestigious national/international conferences with the aid of several travel awards and research fundings that I attained independently throughout my career, which has augmented my communication and collaboration skills. I have always believed that “education goes beyond the formal delivery setting,” and thus, with limited teaching opportunities, I have found ways to teach/ mentor students in laboratory research and remote learning settings.

Performing Laboratory experiment, Boston University, USA (2020).

education goes beyond the formal delivery setting

Presenting my work at an International Human Proteome Organization (HUPO) conference, Madrid, Spain (2014).

My graduate and postdoctoral research career has set the stage to pursue an independent career to address complex bioanalytical chemistry and neurobiology questions. I have recently been awarded my first fellowship grant as an independent principal investigator from the Bright Focus Foundation. I intend to investigate the role of extracellular matrix components in Alzheimer’s disease (AD). I plan to expand further my findings and accomplishments from this project with the aid of successful future grant applications to solve major challenges in AD, expedite clinical and translational research and discovery, uncover therapeutic options, and build a knowledge base. My long-term career objective is to establish an analytical glycobiology research group focusing on unraveling the biomolecular deregulations in neurodegenerative disorders, specifically AD. I am confident that with my strong theoretical and practical background, research expertise in biochemistry and analytical chemistry, and a multidisciplinary profile, I will contribute to society’s welfare and strengthen scientific research and discovery to improve patient health and quality of life.


Written by: Manveen K. Sethi

Edited by: Govinda Raju Yedida (Volunteer, Bio Patrika)

Job opening in Novartis India, Hyderabad

Position: Senior Scientist

Job Description
Plan and perform scientific experiments (or pilot plant processes) for the preparation and timely delivery of drug substances (DS), drug products (DP), processes and procedures in collaboration within a multifunctional project team coordinated by a Project leader. Contribute to maintenance of lab instruments/infrastructure.

Your responsibilities include, but are not limited to:
1. Meet quality, quantity and timelines in all assigned projects; Perform and document scientific experiments; Plan & organize scientific experiments under minimal guidance from more experienced team members. Seeks proactively for support and coaching from Project Leader, Scientific Expert or other team members during the whole process if necessary.
2. Provide documentation of raw data; Evaluate and Contribute to interpretation and report results under minimal guidance from more experienced team members. ; Propose and provide input for the design of next experiments. ; Optimize existing methods (lab or plant) or contribute to new method development and reproduce published methods and develop more efficient ones.
3. Generate lab procedures, reports and/or instructions and/or SOP’s. (I, N) ; Actively transfer procedures/instructions to pilot plant or production, including troubleshooting, process steering controls etc.

  • Communicate and address problems, perform safety and literature searches under moderate guidance from more experienced team member.

4. Keep record of and manage chemicals, intermediates, excipients and solvents within own area of responsibility.
5. Collaborate with other team members to facilitate deliveries of DS and/or DP. ; Act as mentors for new joinees.
6. Utilize special tools/equipments and/or specialized facilities e.g., containment/ sterile labs. ; Evaluate new lab equipment. ; Schedule and perform routine maintenance and calibration of lab instruments/equipment & contribute to maintenance of infrastructure/equipment.
7. Actively participate in project teams/meetings/networks. ; Actively contributes to team goals.
8. Ensure all own activities are aligned with overall drug development process. (B) ; Work according to appropriate SOPs, GMP, GLP, QM, HSE, ISEC & Novartis Guidelines ;Strategic and scientific contribution to Networks, target achievements according to net-work charter and annual objectives.

Minimum Requirements

1. PhD on technical subject with 4 years of industrial or relevant experience. or Master of Science with 8 years of relevant experience Fluency in English language.
2. Awareness for safe handling of chemicals, potentially dangerous materials and equipment. Broad theoretical and scientific knowledge in the relevant area (e.g. manufacturing, analytical, pharmaceutical).
3. Skilled scientist with expertise on LCMS and MS/MS analysis including structural elucidation and characterization of impurities, trace level quantification as well as data interpretation.
4. Experience on dealing OOS/OOE and deviations involving above mentioned analytical techniques.
5. Proficient with laboratory and/or technical tools. Good knowledge of software and computer tools.
6. Good documentation skills.
7. Good knowledge of current Good Manufacturing Practices (cGMP) ;Advanced scientific/technical writing skills Wide experience on de-formulation studies of the drug products , especially in the microscopic evaluation of drug component.

Apply here: https://www.linkedin.com/jobs/view/2356049717/

Job opening in Beckman Coulter

Position: Development Scientist (Assay Development – Flow Cytometry)

Summary of responsibilities:

Assists in the evaluation and implementation of new technologies. The incumbent performs experiments, analyzes data and plans next series of experiments, takes ownership for the assigned work participates in planning studies for the development, evolution and optimization of assay(s);

Prepares study plans and reports, maintains well organized laboratory notebooks in compliance with relevant procedures; and supports post-launch to resolve performance and/or quality issues.

Boundary Conditions/Authority Levels:

Normally receives no instruction on routine work; general instructions on new assignments. Adheres to policies and procedures.

Essential Duties and Responsibilities: include the following. Other duties may be assigned.

  • Participates in the analysis, design and development of system applications.
  • Follows standard practices and procedures in analyzing situations or data from which answers can be readily obtained.
  • Reports status of experiments to supervisor/Technical lead.
  • Applies analytical skills to interpret data and uses independent judgment and discretion in developing solutions to a variety of work problems of moderate scope and complexity
  • Able to troubleshoot issues, identify root cause and strive towards solutions for identified problems
  • Responsible for creating technical presentations and updating relevant functions on the same
  • Responsible for generating high quality technical documents and reports
  • Responsible for strict adherence to quality standards and regulatory guidelines
  • Responsible for communicating business related issues or opportunities to next management level.
  • Responsible for ensuring personal and company compliance with all Federal, State, local and company regulations, policies and procedures for Health, Safety and Environmental compliance.
  • Performs other related duties as required.

Education and/or Experience:

PhD in Life Sciences/Microbiology/ Biochemistry/Biotechnology or relevant fields with 2+ years of experience ; Master’s degree in Microbiology/ Biochemistry/Biotechnology or relevant fields with 5+ years of relevant experience in industry.

Industrial experience in the field of assay development of Flow cytometry reagents, ELISAs or other Immunological techniques is desirable but not mandatory.

Apply here: https://www.linkedin.com/jobs/view/2413491499/