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• M.Sc. (Medical Biochemistry)

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Research Summary

• 2022 2022
• 2023 2023
• 2024 2024

1. Atherosclerosis: Research Reveals New Mechanism and Therapeutic Target

   New research offers fresh insights into how a type of immune cell can destabilize the fatty deposits, or plaques, that form in arteries during atherosclerosis. Healthy arteries keep the heart healthy. A new study may help prevent atherosclerosis — a disease that affects our blood vessels.

   Atherosclerosis is a persistent, inflammatory condition in which plaques build up inside arteries, causing them to narrow and restrict blood flow. When an atherosclerotic plaque bursts or breaks, it can trigger a heart attack or stroke.

   Neutrophils are an abundant type of leukocyte (white blood cell) that defend against infection by attacking microbes. They also serve "many roles in inflammation." The new international study reveals that neutrophils can aggravate atherosclerosis by triggering a previously unknown type of cell death that destabilizes arterial plaques.

   A recent Nature paper describes how neutrophils can induce a series of molecular events that also kills the smooth muscle cells that help to retain the plaques in the artery wall. "Every inflammatory reaction," says co-corresponding study author Prof. Oliver Söhnlein, from the Institute for Cardiovascular Prevention at the Ludwig Maximilian University (LMU) of Munich in Germany, "results in some collateral damage, because neutrophils also attack healthy cells."

   He and his colleagues have also designed and made a "tailored peptide" that could potentially target and block the cell-death process.

2. Embryo Stem Cells Created from Skin Cells

   Researchers at the Hebrew University of Jerusalem (HU) have found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos. The work (in mouse cells) has significant implications for modelling embryonic disease and placental dysfunctions, as well as paving the way to create whole embryos from skin cells.

   As published in Cell Stem Cell, Dr. Yossi Buganim of HU's Department of Developmental Biology and Cancer Research and his team discovered a set of genes capable of transforming murine skin cells into all three of the cell types that comprise the early embryo: the embryo itself, the placenta and the extra-embryonic tissues, such as the umbilical cord. In the future, it may be possible to create entire human embryos out of human skin cells, without the need for sperm or eggs. This discovery also has vast implications for modelling embryonic defects and shedding light on placental dysfunctions, as well as solving certain infertility problems by creating human embryos in a petri dish.

   Back in 2006, Japanese researchers discovered the capacity of skin cells to be "reprogrammed" into early embryonic cells that can generate an entire fetus, by expressing four central embryonic genes. These reprogrammed skin cells, termed "Induced Pluripotent Stem Cells" (iPSCs), are similar to cells that develop in the early days after fertilization and are essentially identical to their natural counterparts. These cells can develop into all fetal cell types, but not into extra-embryonic tissues, such as the placenta.

   Now, the Hebrew University research team, headed by Dr. Yossi Buganim, Dr. Oren Ram from the HU's Institute of Life Science and Professor Tommy Kaplan from HU's School of Computer Science and Engineering, as well as doctoral students Hani Benchetrit and Mohammad Jaber, found a new combination of five genes that, when inserted into skin cells, reprogram the cells into each of three early embryonic cell types -- iPS cells which create fetuses, placental stem cells, and stem cells that develop into other extra-embryonic tissues, such as the umbilical cord. These transformations take about one month.

   The HU team used new technology to scrutinize the molecular forces that govern cell fate decisions for skin cell reprogramming and the natural process of embryonic development. For example, the researchers discovered that the gene "Eomes" pushes the cell towards placental stem cell identity and placental development, while the "Esrrb" gene orchestrates fetus stem cells development through the temporary acquisition of an extra-embryonic stem cell identity.

   To uncover the molecular mechanisms that are activated during the formation of these various cell types, the researchers analyzed changes to the genome structure and function inside the cells when the five genes are introduced into the cell. They discovered that during the first stage, skin cells lose their cellular identity and then slowly acquire a new identity of one of the three early embryonic cell types, and that this process is governed by the levels of two of the five genes.

   Recently, attempts have been made to develop an entire mouse embryo without using sperm or egg cells. These attempts used the three early cell types isolated directly from a live, developing embryo. However, HU's study is the first attempt to create all three main cell lineages at once from skin cells. Further, these findings mean there may be no need to "sacrifice" a live embryo to create a test tube embryo.

3. End to Aids in Sight as Huge Study Finds Drugs Stop HIV Transmission

   An end to the Aids epidemic could be in sight after a landmark study found men whose HIV infection was fully suppressed by antiretroviral drugs had no chance of infecting their partner.

   The success of the medicine means that if everyone with HIV were fully treated, there would be no further infections.

   Among nearly 1,000 male couples across Europe where one partner with HIV was receiving treatment to suppress the virus, there were no cases of transmission of the infection to the HIV-negative partner during sex without a condom. Although 15 men were infected with HIV during the eight-year study, DNA testing proved that was through sex with someone other than their partner who was not on treatment.

   “It’s brilliant – fantastic. This very much puts this issue to bed,” said Prof Alison Rodger from University College London, the co-leader of the paper published in the Lancet medical journal. Earlier studies have also shown the treatment protects heterosexual couples where one partner has HIV.

   She added: “Our findings provide conclusive evidence for gay men that the risk of HIV transmission with suppressive ART [antiretroviral therapy] is zero. Our findings support the message of the international U=U campaign that an undetectable viral load makes HIV untransmittable.”

   “This powerful message can help end the HIV pandemic by preventing HIV transmission, and tackling the stigma and discrimination that many people with HIV face. Increased efforts must now focus on wider dissemination of this powerful message and ensuring that all HIV-positive people have access to testing, effective treatment, adherence support and linkage to care to help maintain an undetectable viral load.”

   In 2017, there were almost 40 million people worldwide living with HIV, of whom 7 million were on antiretroviral treatment. An estimated 101,600 people are living with HIV in the UK, and of these, about 7,800 are undiagnosed, so do not know they are HIV positive.

   Myron S Cohen of the UNC Institute for Global Health and Infectious Diseases at Chapel Hill in North Carolina, said in a commentary in the Lancet on the study that it should push the world forward on a strategy to test and treat everyone who has HIV. But, he added, maximising the benefits of treatment, particularly for men who have sex with men, has proved difficult.

   “It is not always easy for people to get tested for HIV or find access to care; in addition, fear, stigma, homophobia and other adverse social forces continue to compromise HIV treatment,” he said. “Diagnosis of HIV infection is difficult in the early stages of infection when transmission is very efficient, and this limitation also compromises the treatment as prevention strategy.”

   According to the National Aids Trust, 97% of people on HIV treatment in the UK have an undetectable level of the virus, meaning they cannot pass it on. “Hearing this can be enormously empowering and reassuring to people living with HIV,” said Deborah Gold, the trust’s chief executive.

   The latest findings reinforce the importance of people taking HIV tests frequently, which could ultimately end the transmission of the virus altogether in the future. New diagnoses have been declining since their peak in 2005, with figures from 2017 showing a 17% drop on 2016 and a 28% fall compared with 2015.

   Late diagnosis remains a major challenge, still accounting for about 43% of new HIV diagnoses. This disproportionately affects certain groups, including black African heterosexual men and people aged 65 and older.

   “If we don’t reduce late diagnosis, there will always be those who are not aware of their HIV status and who therefore cannot access treatment,” said Gold. “We think that the findings from this study could be incredibly powerful in breaking down some of the barriers to testing in communities where there is still a lot of stigma around HIV.”

   However, she added that government funding cuts to specialist health services would make it more difficult to achieve a goal of eliminating transmission by 2030.

   Jens Lundgren, a professor of infectious diseases at Rigshospitalet, University of Copenhagen, and joint-lead for the study, called Partner, said: “We have now provided the conclusive scientific evidence for how treatment effectively prevents further sexual transmission of HIV.”

   Dr Michael Brady, the medical director at the Terrence Higgins Trust, said: “It is impossible to overstate the importance of these findings. The Partner study has given us the confidence to say, without doubt, that people living with HIV who are on effective treatment cannot pass the virus on to their sexual partners. This has incredible impact on the lives of people living with HIV and is a powerful message to address HIV-related stigma.”

   Bruce Richman, the founding executive director of the Prevention Access Campaign, which launched U=U, said Pac was tremendously grateful to the researchers and participants. He said the study “has forever changed what it means to live and love with HIV around the world.”

   In a linked comment in the journal, Cohen expressed optimism for future treatment of Aids. “During the course of these studies, antiretroviral drugs have become more effective, reliable, durable, easier to take, well tolerated and much less expensive,” he said. “The results … provide yet one more catalyst for a universal test-and-treat strategy to provide the full benefits of antiretroviral drugs. This and other strategies continue to push us toward the end of Aids.”

   Case Study

   Alex Sparrowhawk, 34, has been living with HIV for almost 10 years. When he was diagnosed in November 2009, he had two major concerns: how being HIV positive would impact his work as a financial analyst, and what it meant for future relationships.

   “I was single at the time,” he said. “Just navigating what to do – when to tell people and how to talk to people was really difficult.”

   Alex immediately began antiretroviral treatment, initially taking four pills a day, which was reduced to one pill once his viral load came down to undetectable levels several months later. The latest results confirm that for the past nine years, he has not been able to transmit the virus to anyone, although at the time, medical advice was less definitive.

   Between his diagnosis and now, Alex spent six-and-a-half years in a relationship, and said the possibility – however tiny – of transmitting HIV to his partner was a source of anxiety. “You’d be told it was very unlikely, or that it was only possible under certain circumstances like having an STI,” he said. “But you’re constantly worried about these caveats and you go through this worry together. Now we can say zero risk, which is just so much more empowering for people. It’s a huge weight off your shoulders.”

   Alex hopes the findings will help transform public attitudes about HIV, bringing them in line with medical evidence. “A lot of stigma is driven by fear of being exposed to HIV,” he said. “People still think you can get it from kissing and casual contact. If more people knew about this study, this would change.”

Research Highlights: New Insecticide Resistance Mechanism in Mosquitoes

1. Date: December 26, 2019
2. Reviewed By: James Ives, M.Psych. (Editor)
3. Institution: Liverpool School of Tropical Medicine (LSTM)
4. Discovery: Identification of a new mechanism of insecticide resistance in malaria-carrying mosquitoes.
5. Species Studied:
   • Anopheles gambiae
   • Anopheles coluzzii
6. Key Finding: A particular family of binding proteins in the insect's legs is highly expressed in resistant populations.
7. Protein Identified: SAP2
   • Elevated in resistant populations.
   • Further increased following contact with pyrethroids (the insecticide used on bed nets).
   • Reduction of SAP2 levels restores susceptibility to pyrethroids.
   • Elevated levels of SAP2 induce resistance to pyrethroids in previously susceptible mosquitoes.
8. Implications:
   • Potential target for future additives to bed nets to overcome resistance.
   • Discovery of new resistance mechanisms highlights the need for identifying additional synergists to restore susceptibility.
9. Current Interventions: Introduction of new insecticide-treated bed nets containing piperonyl butoxide (PBO) in addition to pyrethroids.
   • PBO targets one of the most potent resistance mechanisms caused by cytochrome P450s.
10. Quote from Dr. Victoria Ingham: "We have found a completely new insecticide resistance mechanism that we think is contributing to the lower than expected efficacy of bed nets. The protein, which is based in the legs, comes into direct contact with the insecticide as the insect lands on the net, making it an excellent potential target for future additives to nets to overcome this potent resistance mechanism."
11. Quote from Professor Hilary Ranson: "Long-lasting insecticide treated bed nets remain one of the key interventions in malaria control. It is vital that we understand and mitigate for resistance within mosquito populations in order to ensure that the dramatic reductions in disease rates in previous decades are not reversed. This newly discovered resistance mechanism could provide us with an important target for both the monitoring of insecticide resistance and the development of novel compounds able to block pyrethroid resistance and prevent the spread of malaria."

1. Year: 2020
2. Research Focus: Link between severe COVID-19 cases and genetic mutations or auto-antibodies that attack the body.
3. Key Findings:
   • Some life-threatening COVID-19 cases are traced to weak spots in patients' immune systems.
   • At least 3.5% of study patients with severe COVID-19 have mutations in genes involved in antiviral defense.
   • At least 10% of patients with severe COVID-19 produce "auto-antibodies" that attack their own immune system, instead of fighting the virus.
   • Results published in Science on September 24, 2020.
   • 101 out of 987 patients with severe COVID-19 had these harmful auto-antibodies.
4. Implications:
   • Immediate implications for diagnostics and treatment.
   • Testing for auto-antibodies is recommended for patients who test positive for COVID-19.
   • Removing these antibodies from the blood could potentially ease symptoms of the disease.
5. Quote from Jean-Laurent Casanova: "Seeing these harmful antibodies in so many patients was a stunning observation. These two papers provide the first explanation for why COVID-19 can be so severe in some people, while most others infected by the same virus are okay."

Global Efforts in COVID-19 Research

1. Initial Study Start: February
2. Research Team: Casanova's team, in collaboration with global clinicians
3. Study Focus: Investigating severe COVID-19 cases in young people to identify underlying immune system weaknesses.
4. Genomic Analysis Plan:
   • Scan patients' genomes, focusing on 13 genes involved in interferon immunity against influenza.
   • Interferon molecules act as the body’s defense system, detecting and responding to viruses and bacteria.
   • Previous discoveries showed mutations hindering interferon production and function, increasing vulnerability to pathogens.
5. Study Progress:
   • Initial goal: Enroll 500 patients with severe COVID-19 worldwide.
   • By August, over 1,500 patients were enrolled; now more than 3,000.
   • Found harmful mutations in 23 out of 659 patients, affecting antiviral interferons.
6. Key Findings:
   • Some patients with severe COVID-19 have auto-antibodies that attack interferon proteins.
   • 101 out of 987 patients with life-threatening COVID-19 had these auto-antibodies.
   • These antibodies block interferon action and were absent in patients with mild COVID-19 cases.
7. Gender Findings:
   • 94% of patients with harmful auto-antibodies were men.
   • This finding offers an explanation for why men are more likely to develop severe COVID-19.
8. Future Research Directions:
   • Investigate the genetic driver behind the auto-antibodies, potentially linked to X chromosome mutations.
   • Explore clinical trials to test treatments such as interferons not neutralized by the auto-antibodies or plasmapheresis to remove harmful antibodies.
9. Additional Global Efforts:
   • The COVID Human Genetic Effort is looking for genetic factors that might be protective against COVID-19.
   • Recruiting people from households of patients with severe COVID-19 who were exposed but did not develop the disease.
   • "Our lab is currently running at full speed," says Casanova.

Teaching Hours Allotted to Human Biochemistry

Post Graduate (MD)

Integration

The knowledge acquired in biochemistry shall help the students to integrate molecular events with the structure and function of the human body in health and disease.

A total of 38 lectures for Biochemistry are integrated with the following subjects:

• Anatomy
• Physiology
• Pathology
• General Medicine
• OBGY (Obstetrics and Gynecology)
• Pediatrics
• Microbiology

Horizontal Integrated Teaching

Organized by Department (Yearwise)

Conferences/CME/Workshop attended by faculty and students year wise (calendar year) from 1st 2014 to 2019 till date

2020

2021

2022

2023