Discuss the experimental evidence that lead to the discovery of the receptor use

Question

Discuss the experimental evidence that lead to the discovery of the receptor used by the leprosy bacilli to bind to and invade Schwann cells.   Also discuss what are the major effects of leprosy bacteria after it has entered the body and how leprosy changes the properties of the Schwann cells and macrophages to promote its dissemination inside the host

What are induced pluripotent stem cells (IPS)? How are they generated and what can they be used for?   What are some therapeutic potential of the use of IPS?

Discuss the Crispr-Cas9 genome editing technique in detail.   Discuss the experimental evidence showing how editing the CCR5 and CXCR4 receptor using the Crispr-Cas9 technique may lead to resistance to HIV infection and how that may be applied to patients.

Explanation / Answer

1) Schwann cells (SCs) are a major target for infection by M. leprae.It causes nerve injury, demyelination, loss of axonal conductance and disability. PGL-1, a glycoconjugate on the M. leprae surface, binds laminin-2 on Schwan cells. M. leprae also binds to dystroglycan (DG) receptor in schwan cells which has a role in early nerve degeneration. Mycobacterium leprae induced demyelination is due to direct bacterial ligation of neuregulin receptor, ErbB2 and Erk1/2 activation, MAP kinase signaling and proliferation. This process promotes the dissemination of bacteria inside the host.

2) Induced pluripotent stem cells are a type of pluripotent stem cells generated directly from adult cells. They are generated by introducing pluripotency associated genes into the given cells type. Their production is a slow process taking about 3 weeks for human cells. Induced pluripotent stem cells are used in regenerative medicine for replacing lost or damaged cells and tissues. Some of the therapeutic uses are in tissue modelling and drug development, organ synthesis and tissue repair.

3) CRISPR-Cas9 technology enables medical researchers to edit parts of the genome by altering sections of the DNA. The CRISPR-Cas9 system consists of two key molecules that introduce a change into the DNA. These are: an enzyme called Cas9 which acts as molecular scissors that cut the two strands of DNA at a specific location in the genome so that bits of DNA can then be added or removed and a piece of RNA called guide RNA (gRNA). CRISPR-Cas9 has a lot of potential as a tool for treating a range of medical conditions that have a genetic component including cancer.

CCR5 and CXCR4 receptors are involved in the pathogenesis of HIV infection. They are chemokine receptors belonging to family of transmembrane G-protein coupled receptors. They function as coreceptors for HIV. By editing CCR5 and CXCR4 receptors, HIV binding to its receptors are affected thereby preventing its entry and replication inside the cell. Therefore CCR5 antagonists Maraviroc and Aplaviroc and CXCR4 antagonist Plerixafor is used in HIV infected patients to arrest disease progression.

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