Essential Cell Biology Question Bank Pdf

[Ermelindo Klatt]

Researchersat the Broad Institute of MIT and Harvard have uncovered a new form of cell death that is induced by copper. Led by research scientist Peter Tsvetkov and institute director Todd Golub, the team found that copper binds to specialized proteins, causing them to form harmful clumps, and also interferes with the function of other essential proteins. Cells go into a state of toxic stress and ultimately die.

By shedding light on key components of this process, the research also identified which cells are particularly vulnerable to copper-induced death. The findings could help researchers better understand diseases in which copper is dysregulated, and could even inform the development of new cancer treatments. The research is published in Science.

The researchers began systematically testing the hypothesis that the toxicity of the copper carriers stems from copper itself. They showed that many different copper-binding molecules, or ionophores, induced cell death in a similar way, and that this process completely depended on copper availability. Moreover, the researchers found that this form of cell death, which they call cuproptosis, is distinct from other well studied forms. When the researchers blocked known pathways of cell death such as apoptosis and ferroptosis, the cells treated with copper ionophores still died.

Next, the team homed in on how these copper carriers kill cells. They found that cells that relied on mitochondria to produce energy were nearly 1,000 times more sensitive to copper ionophores than cells that use glucose processing. Using multiple CRISPR knockout screens, the team identified key genes that facilitate copper-induced death.

Though one of the copper ionophores, elesclomol, failed its clinical trial as a cancer therapeutic, later analysis revealed that the molecule had helped patients whose tumors rely on mitochondria for energy production. Now that the team has found markers of copper-induced cell death, they suggest that elesclomol could potentially be used to treat a range of cancers that are particularly vulnerable to the process, such as those expressing FDX1.

Tsvetkov is excited by the breadth of these clues and is eager to learn about new organisms or diseases where copper-induced cell death might play a role. He hopes their findings will inspire new research trajectories in cell biology, cancer, and antibiotics.

The Drug Repurposing Hub is one of the most comprehensive and up-to-date biologically annotated collections of FDA-approved compounds in the world. Researchers anywhere can explore more than 6,000 drugs in the hub and search for possible new uses for them to jump-start new drug discovery.

The NeuroGAP-Psychosis project, a collaboration between the Stanley Center for Psychiatric Research and Harvard T.H. Chan School of Public Health to study the genetics of severe mental illness, has recruited more than 42,000 participants in Ethiopia, Kenya, Uganda, and South Africa.

This Canvas shell is created for biology instructors using the OpenStax Microbiology textbook. Each module contains quizzes and activities for one chapter of the textbook. Each quiz is designed to randomly pull 5 questions from a question bank. The activities are created in Canvas new quiz and H5P. Each chapter contains a case study based on the 'Clinical focus' of the chapter in the OpenStax textbook.

Short Description:

The Principles of Biology sequence (BI 211, 212 and 213) introduces biology as a scientific discipline for students planning to major in biology and other science disciplines. Laboratories and classroom activities introduce techniques used to study biological processes and provide opportunities for students to develop their ability to conduct research.

Long Description:

The Principles of Biology sequence (BI 211, 212 and 213) introduces biology as a scientific discipline for students planning to major in biology and other science disciplines. Laboratories and classroom activities introduce techniques used to study biological processes and provide opportunities for students to develop their ability to conduct research. BI211 focuses on how structure defines function in organisms and the pathways and transformation of energy in living systems. BI212 uses genetics as a model system to understand information flow in living organisms. BI213 focuses on the interactions of living systems and the ecology and evolution of biodiversity.

SCHER recognises that there are promising developments that have replaced NHP use. A number of alternative methods (either in vitro or using other animal species) have been developed and implemented over the last decade (e.g. the TgPVR21 transgenic mouse model for neurovirulence and potency testing of poliomyelitis vaccines) (EDQM).

In the opinion of SCHER, animals should only be used in medical research when it is unavoidable and when appropriate and validated alternative methods are not available. Replacing animals in medicine research is a long and difficult process and application of in vitro or in silico methods are often not yet feasible due to highly complex systems and limited knowledge of basic biology and pathophysiology. In addition, experimental models not using animals are often developed in medical research as complementary methods as they may only address questions at sub-cellular or single cell level, or, at best, at the level of interactions between a very limited number of cell types. When whole body integrated systems need to be examined, animal models have to be used in order to better understand the interactions between different cells in an intact organ, and between different organs. The importance of combining all approaches at the cellular, organ and whole body level are vital to a full understanding of the scientific issues.

SCHER also recognises that when animals are used as models of human conditions or as surrogates for humans, there are limitations to the accuracy with which the animal model reflects the pathophysiology, pharmacology or toxicological susceptibility of humans. In the cases examined in this opinion, the use of NHP is considered essential because other species provide demonstrably unsatisfactory models in crucial respects.

It should not be forgotten that humans are also used in experiments whether healthy human subjects, patients participating in clinical studies, and tissues from bio-banks. Furthermore, it is important that there is a constant feedback and iteration between human and animal research, as well as in vitro studies, to improve our knowledge and to make animal and human experiments more meaningful.

In safety testing, regulatory requirements and scientific considerations may almost mandate the use of NHPs if NHPs represent the non-rodent species resembling humans most closely regarding pharmacodynamics and pharmacokinetics. It needs to be noted that testing of new pharmaceuticals in NHPs represents only a very small part of the total safety and efficacy testing. Results obtained in NHPs are introduced into the risk assessment process, which integrates all information from safety testing based on a weight of evidence approach. The total replacement of animals, including NHPs in testing for safety, is not possible based on present knowledge. Arguments against phasing out NHPs in safety testing of pharmaceuticals are therefore identical to those regarding using rodents for toxicity testing, i.e. incomplete knowledge of integrated body systems and pathophysiology, poor representation of pharmacokinetics by in vitro systems, and the absence of NOAEL or benchmark doses vital for human risk assessment (SCHER, 2005).

Regarding safety testing of the highly specific monoclonal antibodies and the other biotechnology derived products, NHPs are often the only relevant model for humans. In certain cases, genetically modified rodents, carrying the human pharmacological target, may replace NHPs. This requires, however, that downstream signalling is relevant for humans and that the alternatives are sufficiently well characterised. At present, genetically modified rodents as well as testing of the homologous protein in rodent species are usually considered as supportive data and not as replacements for the use of NHPs by regulators (Anonymous, 2008).

Micro-dosing is sometimes postulated to be able to replace some animal testing. Microdose studies in humans are considered to be clinical trials in accordance with the EU Clinical Trials Directive and, therefore, have to be supported by animal toxicity studies Therefore, micro-dosing cannot replace animal testing, and administration of chemicals or pharmaceuticals to humans in low doses to study pharmacokinetics and toxicokinetics (biokinetics) (Amberg et al., 1999; Monster et al., 1976) has been used for a long time in research. Recent developments in analytical chemistry such as LC/MS-MS or accelerator mass spectrometry have only refined microdose studies due to more simple sample workup and higher sensitivity. Micro-dosing in early human studies only investigates pharmacokinetics and is performed after administration of very low single doses (max. of 100-fold below the pharmacologically active dose in animals). As a prerequisite for performing microdose experiments in humans, single dose toxicity data in an appropriate animal model are needed to ensure that the microdose given to humans can be considered a safe dose. Thus, toxic effects are not expected in humans and a toxicity profile cannot be established. Toxicity in animals is the relevant endpoint in all safety testing and this can thus not be studied with micro-dosing. However, compounds with an unfavourable human pharmacokinetic profile are not further developed and in that sense, the use of animals in toxicity testing may be reduced due to earlier termination of an unpromising compound. On the other hand, if a compound shows a favourable human pharmacokinetic profile in micro-dosing, all standard animal safety tests are needed for further clinical development, so that micro-dosing in humans can also result in an increase in the number of animals used for a specific compound (single dose toxicity study plus standard tests) (EMEA, 1994).

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