Nepali scholar makes breakthrough in TB

An exciting news published in www.ekantipur.com. Congratulations Prof Lamichhane!!!

KATHMANDU, OCT 03 -2011.

Gyanu Lamichhane, a 35-year-old Nepali researcher at John Hopkins University School of Medicine, has drawn the world several steps closer in finding a better, faster and reliable cure for tuberculosis (TB), which kills over two million people across the globe each year.

His latest findings have paved the way for a much faster approach of weakening the TB causing bacterium, Mycobacterium Tuberculosis, which could potentially shorten TB treatment that now takes at least six months.

In recognition of his achievement, the US government’s National Institute of Health honoured Lamichhane with the coveted New Innovator Award-2011 on September 19 along with a direct funding of $ 1.5 million (Rs 117 million) for his research to be carried out at the university within five years. A statement issued by the Institute on September 19 stated that the award was conferred on Lamichhane and 48 other young scientists for various promising researches in health sciences. 

During his research at Johns Hopkins Centre for Tuberculosis Research, Lamichhane, the assistant professor at the university, discovered what exactly the cell wall of TB causing bacteria is made of. He revealed that the protective cell wall of Mycobacterium Tuberculosis is held together by an enzyme named L,D-transpeptidase. The revelation is said to have come as a breakthrough in the effort to develop medicine that could break the protective wall of the bacterium and thus weaken it and cure the disease altogether.

His research has a key finding that if L,D-transpeptidase is unable to function, Mycobacterium Tuberculosis will have its cell wall weakened and the remaining chemical linkages in the bacterial wall will be an easy target for drugs used in the treatment of TB. Lamichhane now intends to pursue his research on what effect antibiotics will have on L,D-transpeptidase and the possible cure for tuberculosis as well as other bacterial infections.

“My primary interest is the study of genes essential to the growth of mycrobacteria. In future I intend to study the cell division and regulation of cell cycle in mycrobacteria,” Lamichhane told the John Hopkins University publication after receiving the award. He had harboured the dream of finding a cure for TB since 1993, when he was a high school student in Chitwan. In an interview with the Post in 2009, he had stated that his grandfather's death from TB pushed him to find a cure for it.

"My team was doing research with the aim to identify how mycobacterium tuberculosis  grows. We found that an unusual enzyme is required for the bacteria to grow properly and cause disease," he told the Post over telephone from the US on Sunday.

“We have demonstrated what needs to be done to make new drugs. Now the challenge is to work on making drugs and testing them,” he added.

About one third of the world’s population is believed to be infected with M Tuberculosis with 10 million new cases each year.

Tuberculosis is a leading cause of death among those who are infected with both HIV virus and M Tuberculosis, causing for the death of nearly 500,000 people with infections of both.

The complete treatment of tuberculosis requires at least six months for a “short” course treatment. Lamichhane hopes that the findings  will help shorten the treatment duration to mere two weeks.

Lamichhane, who himself suffered from latent tuberculosis, had received a grant worth $ 100,000 from the Bill & Melinda Gates foundation in 2009 for the research on tuberculosis. He was also featured as one of the 36 best and brightest in America by Esquire magazine in 2007.

Key findings

•Lamichhane found what exactly the cell wall of TB causing bacteria is made of

•He discovered that the protective cell wall of Mycobacterium Tuberculosis is held together by an enzyme named L,D-transpeptidase

•Findings to shorten TB treatment duration considerably

A Novel Platform to Investigate G-quadruplex and Ligand Interactions

A collaborative research of the scientists from United States, United Kingdom and Japan has introduced a novel platform to investigate the binding interactions between human telomeric G-quadruplexes and small molecule ligands at single molecule level. This research work has been recently published in Nature Chemistry (link: http://www.nature.com/nchem/journal/v3/n10/pdf/nchem.1126.pdf) which is one of the most reputed Journals in the related field. 

G-quadruplexes are four-stranded nucleic acid secondary structures formed by the guanine rich DNA and RNA sequences. The telomere is one of the critical parts of the eukaryotic chromosomes including those of humans which has propensity to form G-quadruplexes. Telomeres play a vital role in aging and cancer. In normal cells telomere is shortened each time when a cell divides and finally leads to the programmed death of the cell. However in most of the cancer cells, telomere length is maintained because of the over expression of an enzyme called telomerase. The telomerase acts on the telomere and extends its length which makes the cell immortal causing cancer.  The telomeric G-quadruplexes have been proposed to play an important role in the maintenance of telomere because quadruplex structures are not extended by the telomerase. The small molecule ligands have been demonstrated to bind to telomeric G-quadruplexes and suppress telomerase activity. This fact has begun the expansion of telomeric G-quadruplexes into potential therapeutic targets for cancer treatment. Therefore understanding the kinetic, thermodynamic, and mechanical properties of small molecule binding to these structures is important but the classical ensemble assays are unable to measure these properties simultaneously. This novel platform provides the all information at once.

Laser Tweezers to Detect Single Nucleotide Polymorphism

Scientists in the Department of Chemistry, Kent State University have introduced a new novel method to detect Single Nucleotide Polymorphism (SNP) using laser tweezers in microfluidic platform. This work has been published in Journal of the American chemical society (JACS), a leading journal in Chemistry.

SNP is the most common variation in the genomic DNA sequence between members of the same species by one nucleotide. This is caused by various factors. Studies have revealed that they are distributed throughout the human genome by an estimated average of 1 per 1000 base pairs. SNPs are attributed to be closely linked with gene function, genetic variations between individuals, variety of diseases and susceptibilities of humans to the pathogens. Usually SNP is not associated with any disease but it might cause variation in response for the disease, toxins, bacteria, drugs etc. They may be used as bio-markers for disease genes. And, it definitely requires reliable method.

SNPs can be detected by several methods such as molecular beacons, gene sequenceing or some other analytical tools that can detect the difference in effect of a single nucleotide in base pairing with the complementary DNA. The novel idea in the above mentioned publication is the incorporation of the mechanical differentiation of the base pairing event with the microfluidics platform and is expected to be useful in the development of generic biosensors. Laser tweezer was used to monitor the binding of the target DNA sequences with the probe molecule, a DNA hairpin. Binding of the target with the hairpin DNA tied to the tweezers caused hairpin molecule in the unfolded (off) state instead of the stochastic hopping between folded(on ) and unfolded (off) states. Authors had claimed that this method has less background signal compared to fluorescence based technique and easier compared to the PCR based amplification and sequencing techniques. This method has been sensitive enough to detect 100 pM SNP associated with the coronary heart disease.

According to Deepak Koirala, chemistry graduate student and main author of the article who came from Nepal, this innovation is in the process of getting US patent.

Scientists demonstrate that an i-motif and a partially folded structure coexist in the C-rich human ILPR oligonucleotides

Soma N Dhakal in JACS

Scientists from Kent State University have demonstrated that an i-motif and a partially folded structure coexisted in the C-rich human ILPR oligonucleotides using laser tweezers. 

This discovery has recently been published as an article titled ‘Coexistence of an ILPR I-Motif and a Partially Folded Structure with Comparable Mechanical Stability Revealed at the Single-Molecule Level" in JACS.’ Here, ILPR stands for Insulin Linked Polymorphic Region which is human insulin gene. The ILPR region is known to regulate the production of insulin, a hormone which is responsible for the metabolism of glucose. When the control of insulin level fails it causes diabetes. Any stable DNA secondary structure formed in ILPR region may affect the transcription regulation of insulin gene causing insulin related health problems. This clarifies the importance of understanding the stability of DNA secondary structure. According to the main author of the article, Soma N Dhakal, a PhD student at Kent State University chemistry department, they have pioneered the mechanical stability of the tetraplex DNA secondary structure called i-motif formed by the cytosine-rich DNA sequence from the human ILPR.