Kelly Research<\/a> Group has also investigated a possible correlation between inherited mutations of telomerase and blood cancers, specifically myelodysplastic syndrome (MDS), and mutations affecting its function that predispose individuals to developing this form of cancer five to ten years earlier than others without these mutations. While further study could lead to more effective cancer treatment strategies for MDS patients, increasing or decreasing one’s telomere length for health reasons remains premature and possibly harmful at best.<\/p>\nShelterin<\/h2>\n
Stable linear chromosomes depend on having short repetitive DNA sequences at their telomeres which act as buffers against accumulations of damaging double-stranded DNA. Mammals’ telomeres contain characteristic TTAGGG repeat sequences which associate with shelterin protein complex. Shelterin contains six proteins including TRF1, TRF2, RAP1, TIN2, TPP1 and POT1, which form nucleoprotein assemblies to inhibit inappropriate DNA repair processes such as homologous recombination and non-homologous end joining (NHEJ). Human cells with shorter telomeres eventually undergo cell cycle arrest or even cell death; Shelterin plays an essential role in maintaining and segregating them during mitosis.<\/p>\n
Kelly’s group has demonstrated a direct and functional interaction between condensin and POT1, the shelterin component of which directly binds unwound G-rich telomere DNA for Okazaki fragment skipping by human replisome. This leads to DNA repair factors quickly filling lagging-strand gaps, leading to genome instability and ultimately cell death. We have also demonstrated that a conserved structural domain within condensin is critical for recruiting POT1 to unwound telomeres and associating POT1 with t-loops during meiosis and mitosis, respectively. Furthermore, POT1 acts to counteract cohesin so as to enrich condensin at these t-loops before driving their separation in cis during anaphase.<\/p>\n
Telomerase<\/h2>\n
Kelly’s research focuses on understanding the structure and maintenance of telomeres – protective nucleoprotein complexes that cap chromosome ends in eukaryotic cells – through studying their protective nucleoprotein complexes called telomeres. Her group specifically investigates an enzyme called telomerase which counteracts cell division-induced shortening by shortening telomeres; furthermore they aim to uncover whether changes in telomere length correlate with ageing or cancer.<\/p>\n
Scientists were delighted to find in 1998 that expression of the telomerase gene could allow human cell culture cells to continue growing without becoming malignant, sparking much interest among researchers for cell therapy applications. But recently it has come to light that extending cultured cell lives through introduction of telomerase is linked with activating of the c-myc oncogene which is associated with human cancers.<\/p>\n
This finding is significant because it suggests that telomeres may not be the optimal targets for chemotherapy approaches, and that telomerase could actually facilitate tumor growth. Researchers found that c-myc expression levels in immortalized (enabled to grow past their usual senescence point by retrovirus-borne telomerase genes) HMEC cells was two to threefold higher than in cells without this retroviral expression of telomerase gene).<\/p>\n
Though these results are promising, the authors acknowledge that their work is still in an early phase and more research must be completed before using telomerase gene therapy as a therapeutic option for human patients. Furthermore, prolonging healthy cells’ lives through gene therapy approaches such as telomerase could increase their lifespan without necessarily preventing disease or delaying aging.<\/p>\n
There is an industry of companies claiming their products can reverse the effects of aging or even cure diseases like Alzheimer’s. Products range from creams and pills containing the telomerase gene; however, none of these claims are supported by scientific evidence. A recent settlement reached between the Federal Trade Commission and TA Sciences’ CEO Noel Patton revealed this company made misleading or unverifiable anti-ageing claims.<\/p>\n
Cryo-EM<\/h2>\n
Cryo-EM provides scientists with unprecedented access to the complex molecular machinery underlying life. This cutting-edge imaging technique unveils hidden structures of proteins, viruses and cell components with astonishing clarity – revolutionizing structural biology as we know it!<\/p>\n
Cryo-EM experiments involve researchers spreading biological samples such as protein molecules across a grid of tiny holes in carbon film and then submerging it in an ethane and cryogen solution, which freezes water along with any cargo of proteins within it into a glassy state that can be imaged under high-energy electron beams without harming or altering them.<\/p>\n
Cryo-fixation, otherwise known as cryo-EM, allows samples to remain in an inert frozen-hydrated state while being introduced into a high vacuum of an electron microscope without suffering damage from radiation. While conventional EM requires thin specimens at equal resolution for its analysis, cryo-EM allows thick samples up to tens of millimeters thick to be imaged by using plunge freezing or “cryo-focused ion beam milling,” followed by placing thin sections onto an electron microscopy grid for imaging and imaging.<\/p>\n
Cryo-EM has yielded many impressive discoveries in structural biology, such as the atomic-resolution structure of an influenza virus particle and molecular basis for antiviral vaccines. Working alongside Morgridge researcher Paul Ahlquist’s lab at Morgridge, Grant Lab scientists have also shed light on viral polymerase structures involved with coronavirus replication that cause deadly diseases like COVID-19 and SARS-CoV.<\/p>\n
As demand for high-resolution structures increases, structural biologists are employing cryo-EM in combination with other powerful imaging techniques to expand what can be seen at the nanoscale. They use it with the diffraction approach of X-ray crystallography to visualize macromolecular complexes that defy crystallization processes; additionally they leverage new direct electron detectors and software for “cryogenic electron tomography” (cryo-ET), which reconstructs 3D images from tilted 2D images.<\/p>\n