Wednesday, 17 April 2019

New Technology May Help Engineer Natural Proteins In Human Body

The linchpin detaches within physiological conditions and provides unique reactivity for the installation of a probe of interest.

(Research team at Indian Institute of Science Education and Research- Bhopal)

Any machine is an assembly of multiple well-designed and organized components. Their smooth handling requires an understanding of the architecture and toolbox to tune the functions. Likewise, proteins are one of the most important components of the human body or bio-machines.  If we can learn how to engineer proteins with high precision, it could provide a tremendous boost to precision therapeutics.

Now Dr. Vishal Rai’s team at Indian Institute of Science Education and Research Bhopal- provides the first modular platform for precision engineering of native proteins. The study was published in the Journal of the American Chemical Society.

“Initially, our reagent delivers a reversible intermolecular reaction that places the “chemical linchpins” globally on all the accessible Lys amino acid residues. These linchpins can drive precise covalent labelling of proteins. The linchpin detaches within physiological conditions and provides unique reactivity for the installation of a probe of interest,” said Dr. Vishal Rai.

“The technology would provide researchers to install a reporter in a protein for a better understanding of the biological systems. Also, it will help in the development of next-generation protein-based drugs,” he added.

Researchers say this methodology could label even a single protein in a mixture of proteins without altering their structures. The team could successfully label myoglobin, cytochrome C, aldolase, and lysozyme C without changing their enzymatic activity. Interestingly, labelling of insulin did not alter cellular uptake and its downstream signalling process.

This study is promising and linchpin directed modification (LDM) may provide a route for the conjugation of a fluorophore and drug to the antibody for targeted treatments. The study will have a long-term implication on protein-based therapeutics as it enables the regulation of their design.

Besides Vishal Rai research team included Srinivasa Rao Adusumalli, Dattatraya Gautam Rawale, Usha Singh, Prabhanshu Tripathi, Rajesh Paul, Neetu Kalra, Ram Kumar Mishra, Sanjeev Shukla. This interdisciplinary study was supported by the Science and Engineering Research Board (SERB).

Journal Reference:

Monday, 8 April 2019

Scientists Present New Regulatory Clues To Mammalian Cell Division

Hook2 is behaving like linker protein—that binds to dynein and dynactin and regulates the function of dynein during cell division.

(Right To Left) Dr. Mahak Sharma and her lab member.
Indian researchers have revealed regulatory role of a protein in the process of cell cycle progression and separation of newly formed mammalian cells. This study may help understanding uncontrolled cell division related cues because many regulatory proteins of the cell cycle, such as the one that reported in this study, are mutated in cancer cells.

Scientists have known that dynein, a molecular machine- that generates force to move cellular cargo from one location to another, plays a crucial role during the cell division especially in dissolving or breaking nuclear envelope and separation of the chromosomes into two daughter cells. However, how dynein simultaneously performs multiple functions at multiple places largely remains an active area of study.

Dr. Sivaram and Amrita RCB Faridabad
Now in a collaborative study, published in the Journal of Cell Biology, research team of Dr. Mahak Sharma at Indian Institute of Science Education and Research (IISER, Mohali) and Dr. Sivaram V. S. Mylavarapu at Regional Centre for Biotechnology (RCB, Faridabad) - have uncovered the role of dynein binding partner and member of Hook family of protein, Hook2 in regulating specific dynein localization and thereby the tasks associated with these subcellular locations.

“We have been exploring the role of a recently characterized family of proteins known as the “Hook proteins” that bind to dynein and regulate its location and cellular function. Our gene silencing experiments revealed improper cell division upon loss of a Hook family member, and we started to pursue its role in dynein activation and mitosis,” said Dr. Mahak Sharma, Scientist at IISER, Mohali and study leader in this study.

During the separation process of newly formed cells, communication and the material transfer happen by transport of cellular cargo. “The transport itself is executed by the molecular machines or motors that generate force to move cargo on the cellular highways or as scientifically called “microtubule tracks,” explained Devashish Dwivedi, the first-author of the study.

In this study, microscopic imaging of cultured human cells were performed to determine the defects in cell division process when cells were depleted of the dynein or its newly identified regulator. “We observed that Hook2 is behaving like linker protein—that binds to dynein and dynactin and regulates the function of dynein during cell division,” said Dwivedi.

“Earlier studies have reported chromosomal translocations in the Hook protein in various cancer cells. Since unregulated cell division is a hallmark of all cancer cells, our findings might provide a partial explanation of why such changes in Hook2 gene locus might be a contributing factor in governing cancer progression,” added Dr. Sharma.
Besides Sharma M., Dwivedi D, Rathi S from IISER-Mohali, research team included Kumari A and Mylavarapu SVS -from RCB, Faridabad. The study was supported by Wellcome Trust/Department of Biotechnology India Alliance, and Science and Engineering Research Board (SERB), Govt. of India. (SCISOUP)