Category Archives: Biochemistry

About the position

The postdoctoral fellowshipposition is atemporaryposition where the main goal is to qualify for work in senior academic positions.

We are seeking candidates with strong interest in bioengineering holding a PhD degree (or having submitted the PhD thesis) in biotechnology, biochemistry or related fields.

The research activities will be part of the PolySpore project funded by the NovoNordisk Foundation. In the project we will develop novel biological and hybrid materials as well as new data-storage concepts using bacterial spores. The researcher will work on genetically optimizing and manipulating spores of the Gram-positive bacterium Bacillus subtilis to present and produce load bearing proteins and characterize the resulting product, as well as to work on light driven catalysis using enzymes and upconverting nanoparticles.

Some aspects of the project are examined in collaboration with partners from France and Lithuania.

Your immediate leader is Assoc.Prof. Johannes Kabisch.

Duties of the position

Requiredselectioncriteria

The appointment is to be made in accordance withRegulations on terms of employment for positions such as postdoctoral fellow, Ph.D Candidate, research assistant and specialist candidate.

Preferred selection criteria

Personal characteristics

Emphasis will be placed on personal and interpersonal qualities.

Weoffer

Salary and conditions

As a Postdoctoral Fellow (code 1352) you are normally paid from gross NOK 563 500 per annum before tax, depending on qualifications and seniority. From the salary, 2 % is deducted as a contribution to the Norwegian Public Service Pension Fund

The period of employment is 2,5 years.

The engagement is to be made in accordance with the regulations in force concerningState Employees and Civil Servants, and the acts relating to Control of the Export of Strategic Goods, Services and Technology. Candidates who by assessment of the application and attachment are seen to conflict with the criteria in the latter law will be prohibited from recruitment to NTNU.

After the appointment you must assume that there may be changes in the area of work.

The position is subject to external funding.

It is a prerequisite you can be present at and accessible to the institution on a daily basis.

About the application

The application and supporting documentation to be used as the basis for the assessment must be in English.

Publications and other scientific work must follow the application.Please note that applications are only evaluated based on the information available on the application deadline. You should ensure that your application shows clearly how your skills and experience meet the criteria which are set out above.

If, for any reason, you have taken a career break or have had an atypical career and wish to disclose this in your application, the selection committee will take this into account, recognizing that the quantity of your research may be reduced as a result.

The application must include :

If all,or parts,of your education has been taken abroad, we also ask you to attach documentation of the scope and quality of your entire education.Description of the documentation required can befoundhere. If you already have a statement from NOKUT,pleaseattachthisas well.

Joint works will be considered. If it is difficult to identify your contribution to joint works, you must attach a brief description of your participation.

In the evaluation of which candidate is best qualified, emphasis will be placed on education, experienceand personal and interpersonalqualities.Motivation,ambitions,and potential will also countin the assessment ofthe candidates.

NTNU is committed to following evaluation criteria for research quality according toThe San Francisco Declaration on Research Assessment - DORA.

General information

Working at NTNU

NTNU believes that inclusion and diversity is a strength. We want our faculty and staff to reflect Norways culturally diverse population and we continuously seek to hire the best minds. This enables NTNU to increase productivity and innovation, improve decision making processes, raise employee satisfaction, compete academically with global top-ranking institutions and carry out our social responsibilities within education and research. NTNU emphasizes accessibility and encourages qualified candidates to apply regardless of gender identity, ability status, periods of unemployment or ethnic and cultural background.

The city of Trondheimis a modern European city with a rich cultural scene. Trondheim is the innovation capital of Norway with a population of 200,000.The Norwegian welfare state, including healthcare, schools, kindergartens and overall equality, is probably the best of its kind in the world. Professional subsidized day-care for children is easily available. Furthermore, Trondheim offers great opportunities for education (including international schools) and possibilities to enjoy nature, culture and family life and has low crime rates and clean air quality.

As an employeeatNTNU, you mustat all timesadhere to the changes that the development in the subject entails and the organizational changes that are adopted.

A public list of applicants with name, age, job title and municipality of residence is prepared after the application deadline. If you want to reserve yourself from entry on the public applicant list, this must be justified. Assessment will be made in accordance withcurrent legislation. You will be notified if the reservation is not accepted.

If you have any questions about the position, please contact Assoc.Prof. Johannes Kabisch, email: johannes.kabisch@ntnu.no.

If you think this looks interesting and in line with your qualifications, please submit your application electronically via jobbnorge.no with your CV, diplomas and certificates attached. Applications submitted elsewhere will not be considered.Upon request, you must be able to obtain certified copies of your documentation.

Application deadline: 17.10.2022

NTNU

NTNU - knowledge for a better world

The Norwegian University of Science and Technology (NTNU) creates knowledge for a better world and solutions that can change everyday life.

Department of Biotechnology and Food Science

Our activities contribute to increased exploitation of existing and new ingredients for sustainable food production as well as next-generation energy solutions and medical technology. We educate graduates for a wide range of careers in industry, public administration and academia.The Department of Biotechnology and Food Scienceis one of eight departments in theFaculty of Natural Sciences.

Deadline17th October 2022EmployerNTNU - Norwegian University of Science and TechnologyMunicipalityTrondheimScopeFulltimeDuration TemporaryPlace of service Glshaugen

Read more:
Postdoctoral Fellowship in Synthetic Biology job with NORWEGIAN UNIVERSITY OF SCIENCE & TECHNOLOGY - NTNU | 309904 - Times Higher Education

JERUSALEM, Sept. 19, 2022 /PRNewswire/ -- The Hadassah Cancer Research Institute (HCRI) at the Hadassah University Medical Center in Jerusalem, announced today that it is leading CancerRNA (www.cancerna.info), a global consortium that aims to apply RNA-based therapeutics to successfully unlock anti-cancer immune responses. While RNA-based therapies, namely mRNA vaccines, shined during the pandemic and saved millions of lives, they have yet to be successfully tested in cancer therapies. The HCRI hosted the opening meeting and workshops of CancerRNA in Jerusalem this month to plan, collaborate and advance the aims of this groundbreaking international consortium to impact the future of cancer treatment.

The CanceRNA team, led by Professor Michal Lotem, MD, Head of HCRI, the Center for Melanoma and Cancer Immunotherapy, and Prof. Rotem Karni Department Chair at Biochemistry and Molecular Biology, Hebrew University-Hadassah Medical School, will focus on two main goals. First, will be harnessing the modulation of RNA processing to increase the immunogenicity of "cold" cancers which lack genomic mutations, to exploit abnormal transcripts and evoke immune response; and second, enhancing the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors and developing personalized mRNA vaccines.

This multi-disciplined team is composed of international leaders in the fields of RNA research, clinicians and biotech-pharma experts in RNA processing, RNA drug design and delivery, biocomputing and immuno-oncology: Wolf Prize Laureate Prof. Lynne Maquat of the University of Rochester; Prof. Maria Carmo Fonseca of the University of Lisbon; Prof. Juan Valcarcel of the Center for Genomic Regulation in Barcelona; Prof. Tanja DeGruijl of the University of Amsterdam; Prof. Niels Schaft of the University of Erlangen; Erez Levanon of Bar Ilan University; Seth Salpeter of Immunyx; Pablo Menendez of Jose Carreras Leukemia Institute in Spain; Evelien Smits of the University of Brussels; and Regine Shevach, Simon Geissler and Daniel Helman of Merck.

"CanceRNA will initially focus on two cancer types, acute myeloid leukemia, relevant for pediatric cancer, and uveal melanoma, both of which harbor splicing factor mutations and that are generally refractory to immunotherapy," said Professor Lotem. "Our hope is to utilize RNA-based therapeutics to overcome what until now, have been key barriers to successful anti-cancer immune responses. "

"The combination of experts from all over Europe in the fields of RNA biology, immunology, bioinformatics and drug transport will propel the development of the next generation of immunotherapy cancer treatments," added co-CanceRNA leader, Professor Rotem Karni, Chair of the Biochemistry and Molecular Biology Department at the Hebrew University-Hadassah Medical School.

Visit http://www.cancerna.info, for more information on CanceRNA.

About CanceRNA:

CanceRNA aims to impact the future of cancer treatment by developing and validating novel RNA-based therapeutics. This three-year project comprises multi-disciplinary activities to assess in-vitro and in-vivo validation, bioinformatics, delivery, and safety based on new and effective modalities of immunotherapy for cancer treatment. The CanceRNA team of researchers and scientists will be harnessing the modulation of RNA processing to enhance the accessibility and immune susceptibility of the tumor and its microenvironment, while working to enhance the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors and developing personalized mRNA vaccines. For more information, http://www.cancerna.info.

About the Hadassah Cancer Research Institute:

Hadassah Cancer Research Institute (HCRI) is a translational research arm of Hadassah Medical Organization and Sharett Cancer Center in Jerusalem. Discoveries made in HCRI labs are a driver of clinical progress and beyond. With advanced labs focused on excellence areas of research in: Immuno Oncology, Cancer Epigenetics, Early Cancer Detection, Cell Therapy, Bioinformatics and a Biobank, our physicians and researchers are developing a multi-disciplined, multi-institution approach to discovering the next-generation treatments to fight cancer.

For additional information on the Hadassah Cancer Research Institute and CanceRNA, contact:

Amalia Herszkowicz, Chief Operating Officer, HCRI, Communication Officer, CanceRNAHadassah Cancer Research Institute (HCRI)[emailprotected]

View original content:https://www.prnewswire.com/news-releases/breakthrough-rna-based-anti-cancer-immunotherapy-treatments-being-developed-by-global-consortium-led-by-the-hadassah-cancer-research-institute-301627084.html

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Breakthrough RNA-Based Anti-Cancer Immunotherapy Treatments Being Developed by Global Consortium led by the Hadassah Cancer Research Institute -...

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New research evaluates how rapid tests will perform when challenged with future SARS-CoV-2 variants.

The availability of rapid antigen tests has significantly advanced efforts to contain the spread of COVID-19. But every new variant of concern raises questions about whether diagnostic tests will still be effective.

The new study in Cell attempts to answer these questions.

The researchers developed a novel method for evaluating how mutations to SARS-CoV-2 can affect recognition by antibodies used in rapid antigen tests.

Because most rapid antigen tests detect the SARS-CoV-2 nucleocapsid protein (N protein), the team directly measured how mutations to the N protein affected diagnostic antibodies ability to recognize their target.

Based on our findings, none of the major past and present SARS-CoV-2 variants of concern contain mutations that would affect the capability of current rapid antigen tests to detect antibodies, says first author Filipp Frank, an assistant professor in the department of biochemistry at Emory University. Further, these data allow us to look one step ahead and predict test performance against almost any variant that may arise.

The study used a method called deep mutational scanning to evaluate all possible mutations in the N protein in a single, high-throughput experiment. Researchers then measured the impact of the mutations on their interaction with antibodies used in 11 commercially available rapid antigen tests and identified mutations that may allow for antibody escape.

Accurate and efficient identification of infected individuals remains a critically important strategy for COVID-19 mitigation, and our study provides information about future SARS-CoV-2 mutations that may interfere with detection, says senior study author Eric Ortlund, a professor in the department of biochemistry. The results outlined here can allow us to quickly adapt to the virus as new variants continue to emerge, representing an immediate clinical and public health impact.

Findings show that its relatively rare for variants to have mutations to the N protein that allow them to evade diagnostic tests, but there are a small proportion of sequences that could affect detection. Researchers, public health officials, and test manufacturers can use these data to determine if a diagnostic test needs to be evaluated for its ability to detect these mutations or to inform future test design.

Considering the endless cycle of new variants, the data from this study will be useful for years to come, says Bruce J. Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and lead for the Rapid Acceleration of Diagnostics (RADx) Tech program at National Institutes of Health.

While many variants of concern contain multiple mutations to the N protein, the study authors note that their method does not evaluate how multiple mutations could affect diagnostic antibody recognition, representing a limitation of the study.

Support for the project came from NIBIB as part of the RADx initiative.

Source: Emory University

Read more here:
Will rapid COVID tests be able to detect new variants? - Futurity: Research News

DPPH scavenging and metal chelating activity of sage

In order to support the protective role of sage against uranyl acetate toxicity, DPPH scavenging and metal chelating activities, which indicate antioxidant activity, were investigated and the results are given in Fig.2. DPPH is a stable free radical in aqueous solutions, and the decrease in the absorbance of the DPPH radical indicates antioxidant activity. Sage was determined to exhibit a dose-dependent increasing DPPH scavenging effect. DPPH scavenging activities of 200mg/mL sage, BHA and BHT were determined as 72.9%, 67.9% and 89.1%, respectively. The metal chelating activities of sage and standards were determined by evaluating their ability to compete with ferrozine for the ferrous ions. A dose-dependent increasing activity was also obtained in metal chelating activity. Metal chelating activities of 200mg/mL sage, BHA and BHT were determined as 82.8%, 76.3% and 88.5%, respectively. These results show that sage has a free radical scavenging activity that is higher than the standard antioxidant BHA and lower than BHT. Its high DPPH removal and metal chelating activity indicate the antiradical and metal chelating properties of sage, as well as its strong antioxidant capacity. There are also studies in the literature that draw attention to the similar features of sage. Emre et al.30 reported that different Salvia species grown in Turkiye exhibited metal chelating activity in the range of 45.080.48%. Roman et al.31 investigated the antiradical properties of S. officinalis extract and stated that it exhibited more than 85% DPPH removal activity. With the powerful antioxidant property, Sage has a protective role against much toxicity, and the results obtained in the Allium test in this study confirm this hypothesis.

DPPH scavenging (DSCA) and metal chelating activity (MCA) of sage.

The effects of uranyl acetate and sage application on selected physiological parameters are shown in Table 1. The maximum germination percentage, root length and weight gain were measured in the control group and Group II and Group III, which were exposed to two different doses of sage. No statistically significant difference was found between the physiological parameter values measured in these groups (p>0.05). In Group IV, in which 0.1mg/mL of uranyl acetate was administered, statistically significant decreases were found in all investigated physiological parameter values compared to the control group (p<0.05). It was observed that this decrease was approximately 2.1 times for germination percentage, about 7 times for root length and about 4.8 times for weight gain. The application of sage together with uranyl acetate caused a statistically significant (p<0.05) increase in the values of all investigated physiological parameters, although not as much as the control group. It was determined that these increases were more pronounced at the 380mg/L dose of sage. Compared to Group IV, germination percentage increased approximately 1.2 times, root length approximately 1.9 times and weight gain approximately 1.8 times in Group VI.

Although there is no comprehensive study in the literature on the effects of uranium or uranyl acetate application on the physiological properties of plants, there are some studies on the effects of other heavy metals. For example, avuolu et al.32 determined that Pb and Hg heavy metal application at 10 and 50ppm doses caused dose-dependent decreases in the germination percentage, root length and weight gain of Cicer arietinum L. seeds. They also reported that these decreases were more pronounced in the group exposed to the 50ppm dose of Hg. avuolu and Yaln33 determined that 25 and 50ppm doses of Al and Co application caused a dose-dependent decrease in the germination percentage, root length and weight of Phaseolus vulgaris L. cv. kidney bean seeds. They also observed that these decreases were more pronounced at the 50ppm dose of Al. Grel et al.34 observed that 2.4, 8.0 and 12.5mg/L Cr doses caused dose-related decreases in germination percentage, root length and weight gain in A. cepa. Girasun et al.35 determined that Pb application at 50, 100 and 200mg/L doses caused a dose-dependent decrease in physiological parameters such as germination percentage, root length and weight gain in A. cepa. Macar et al.36 found statistically significant reductions in germination percentage, root length and weight gain in A. cepa bulbs exposed to 5.5mg dose of Co for 72h.

In this study, it is thought that the abnormalities in physiological parameters as a result of uranium exposure are due to the reduction of A. cepa roots' intake of water and inorganic substances. Because it has been reported in the literature that high doses of heavy metal exposure in different plant species reduce the water and mineral substance uptake of the roots, and their productivity decreases by affecting the photosynthesis reactions and nitrogen metabolisms. On the other hand, it has been reported that exposure to heavy metals causes root, shoot, plant growth and plant weight reduction, deterioration of grana structure, inhibition of chlorophyll synthesis and respiration and development of apoptosis and necrosis processes in plants. ROS produced by heavy metals is shown as the main reason for the processes that encourage all these negative effects in the plant. Sage, which exhibits strong DPPH removal and metal chelating activity, protected against oxidative stress induced by uranium and exhibited a toxicity-reducing effect with its antioxidant property. It has also been stated in the literature that plants have developed some effective defense mechanisms to combat ROS-induced oxidative stress37. Therefore, it is considered that these defense mechanisms developed by A. cepa to prevent uranium from entering the cell may be another reason for the decrease in the investigated physiological parameter values. Because the excessive increases in the number/frequency of epidermis and cortex cells observed in the microscopic examination of root tip meristematic cells support this idea.

The genotoxicity induced by uranyl acetate application and the protective role of sage against this toxicity are shown in Figs. 3, 4 and Table 2. Statistically insignificant (p>0.05) MN formations were found in the control group and Group II and Group III, which were exposed to two different doses of sage. In addition, CAs in the form of a few sticky chromosome and unequal distribution of chromatin was detected in these groups, which was not statistically significant (p>0.05). On the other hand, the highest MI value (741.30, 747.90 and 743.80, respectively) was also determined in these groups. The application of 0.1mg/mL uranyl acetate caused the highest rate (82.40) of MN formation (p<0.05) in the root tip cells of the bulbs in Group IV, and promoted CAs such as fragment, vagrant chromosome, sticky chromosome, bridge and unequal distribution of chromatin and caused significant decreases (p<0.05) in the MI value. The greatest effect of uranyl acetate application on chromosomes occurred in the form of fragment formation. The application of sage together with uranyl acetate decreased the genotoxic effects of uranyl acetate, and caused a statistically significant (p<0.05) decrease in the frequencies of MN and CAs, and a significant (p<0.05) increase in the MI value, depending on the dose. It was determined that these alterations observed in the investigated genotoxic parameters were more pronounced in Group VI, where 380mg/L dose of sage was administered. Compared to Group IV, the frequency of fragment decreased approximately 1.5 times, the MN frequency decreased approximately 1.4 times, and the MI rate increased approximately 1.3 times in Group VI.

CAs induced by uranyl acetate. MN in interphase (a), fragment in metaphase (b), vagrant chromosome in anaphase (c), sticky chromosome in prophase (d), bridge in early anaphase (e), unequal distribution of chromatin in anaphase (f).

The effects of uranyl acetate and sage on DCN and MI (%). Group I: Control, Group II: 190mg/L sage, Group III: 380mg/L sage, Group IV: 0.1mg/mL uranyl acetate, Group V: 0.1mg/mL uranyl acetate+190mg/L sage, Group VI: 0.1mg/mL uranyl acetate+380mg/L sage. MI was calculated by counting 10,000 cells in each group. *indicates statistical difference between Groups I and IV, **indicates statistical difference between Groups IV and VI (p<0.05). DCN: dividing cell number, MI: mitotic index.

Although there is no comprehensive study in the literature on genotoxicity caused by exposure to uranium or uranyl acetate in plants, there are some studies conducted with experimental animals. For example, avuolu et al.38 observed MN formation in erythrocyte and buccal mucosal epithelial cells of Swiss albino mice exposed to 5mg/kg b.w of uranyl acetate by oral gavage for 5days. In addition, they reported a decrease in MI value with CAs in the form of break, fragment, gap, acentric and ring chromosomes in bone marrow cells. In addition, there are some studies in the literature investigating the genotoxicity induced by other heavy metal ions in plants. For example, avuolu et al.32 determined that exposure to Pb and Hg at two different doses (10 and 50ppm) caused an increase in the frequency of MN in C. arietinum root tip cells and promoted CAs in the form of sticky chromosome and bridge. avuolu and Yaln33 observed that exposure to Al and Co at 25 and 50ppm doses caused MN formation in P. vulgaris cv. kidney bean root cells. Grel et al.34 reported that administration of three different doses of Cr (2.4, 8.0 ve 12.5mg/L) caused a dose-dependent decrease in MI in A. cepa root tip cells. In addition, they found an increase in the frequency of MN and the numbers of CAs such as fragments, unequal distribution of chromatin, sticky chromosomes, bridges, reverse polarization and c-mitosis. Girasun et al.35 showed that exposure to three different doses (50, 100 ve 200mg/L) of Pb decreased the MI value, increased the frequency of MN, and caused damage in the form of fragments, adhesions, bridges and c-mitosis in A. cepa root tip cells, depending on the application dose. Macar et al.36 observed a decrease in MI, an increase in MN formation and an increase in the number of CAs in root tip cells of A. cepa, where 5.5mg of Co was applied. They also determined that Co application promotes CAs in the form of fragment, sticky chromosome, bridge, unequal distribution of chromatin, multipolar anaphase, nucleus damage, and irregular mitosis.

In our study, it is thought that the main reason for the decrease in MI value and the increase in the numbers of MN and CAs in Group IV treated with uranyl acetate may be due to the direct or indirect interaction of uranium with chromosomes. Because it has been reported in the literature that heavy metals disrupts the structure of DNA directly or indirectly by producing ROS, promoting DNA damages. On the other hand, some heavy metals have been reported to cause disruptions in DNA repair processes. For example, while Cr causes damage by reacting directly with DNA, As, Ni and Cd act by preventing the repair processes of DNA double-strand breaks. Damages such as MN, fragments, breaks, sister chromatid exchanges and variation are other CAs promoted by heavy metal ions39. The genotoxic and cytotoxic effects induced by uranyl acetate may be related to the occurrence of oxidative stress in general. Sage protects the integrity of the genome by reducing the oxidative load in the cell, especially with its strong metal chelating activity and antioxidant power. The reductions in MN and CAs frequencies observed in groups V and VI treated with sage+uranyl acetate confirm this idea.

The effects of uranyl acetate and sage application on selected biochemical parameters are shown in Fig.5. No statistically significant difference was observed between the root MDA levels and SOD and CAT activities of the control group and Group II and Group III exposed to two different doses of sage (p>0.05). Uranyl acetate application at 0.1mg/mL dose caused statistically significant (p<0.05) increases in root MDA level, which is an indicator of lipid peroxidation, and in SOD and CAT activities, which are antioxidant enzymes. Compared to the control group, these increases were found to be approximately 3.8 times for MDA level, approximately 3.2 times for SOD activity and approximately 2.7 times for CAT activity in Group IV. It was determined that the application of sage together with uranyl acetate again promoted statistically significant (p<0.05) decreases in MDA levels, SOD and CAT activities, depending on the dose. These decreases were even more pronounced in Group VI exposed to 380mg/L of sage. Compared to Group IV, approximately 2.1-fold decrease in MDA level, approximately 1.3-fold decrease in SOD activity and approximately 1.3-fold decrease in CAT activity was detected in Group VI.

Effect of uranyl acetate and sage application on selected biochemical parameters. Group I: Control, Group II: 190mg/L sage, Group III: 380mg/L sage, Group IV: 0.1mg/mL uranyl acetate, Group V: 0.1mg/mL uranyl acetate+190mg/L sage, Group VI: 0.1mg/mL uranyl acetate+380mg/L sage. * indicates statistical difference between Groups I and IV, ** indicates statistical difference between Groups IV and VI (p<0.05).

Although there is no comprehensive study in the literature of biochemical toxicity induced by exposure to uranium or uranyl acetate in plants, there are some studies with Swiss albino mice. avuolu et al.38 reported a significant increase in blood MDA levels and a significant decrease in GSH levels in Swiss albino mice exposed to 5mg/kg b.w of uranyl acetate by oral gavage for 5days. In a similar study, Yapar et al.40 found significant increases in MDA levels and significant decreases in GSH levels in liver and kidney tissues of Swiss albino mice exposed to 5mg/kg b.w of uranyl acetate. In addition, there are some studies dealing with the biochemical toxicity induced by other heavy metals other than uranium in plants. avuolu et al.32 reported that MDA levels in C. arietinum root tip cells exposed to Pb and Hg heavy metals at 10 and 50ppm doses increased dose-dependently, and these increases were even more pronounced at 50ppm doses of Hg. avuolu and Yaln33 stated that the application of Al and Co at two different doses (25 and 50ppm) caused dose-related increases in the MDA levels of P. vulgaris cv. kidney bean root cells, and these increases were higher et al. doses than at Co doses. Macar et al.36 observed that Co application at 5.5mg dose caused significant increases in MDA levels and SOD and CAT enzyme activities of A. cepa root tip cells.

MDA is a 3-carbon aldehyde, which is one of the most important markers of cell membrane damage, in other words, lipid peroxidation. Lipid peroxidation is a reaction caused by free radicals that cause oxidative damage of unsaturated fats. A free radical can then abstract the H atom and form an oxidized lipid free radical, producing a peroxyl radical. The peroxyl radical can remove an electron and produce a lipid hydroperoxide and another lipid free radical. This process can continue as a chain reaction. Since lipid hydroperoxide is unstable, it decomposes to form MDA and 4-hydroxy-2-nonenal products. In cases where the increase of free radicals in the cell, enzyme systems and antioxidant molecules in the cell are not sufficient for protection, these free radicals attack cell membranes, cause lipid peroxidation and increase MDA levels41. Therefore, the increase in MDA levels in A. cepa root cells treated with uranyl acetate can be explained by the fact that uranium causes free radical production and these free radicals cause damage to the membranes of the root cells.

SOD and CAT enzymes are known as antioxidants that prevent the formation of free radicals in the cell or eliminate or neutralize their effects. While the SOD enzyme neutralizes the superoxide radical, the CAT enzyme catalyzes the conversion of H2O2, which is highly toxic for the cell, into water and oxygen42. Therefore, the increase in SOD and CAT enzyme levels in A. cepa root cells exposed to uranyl acetate can be explained by the fact that uranium causes free radical production and increases SOD and CAT enzyme levels as a defense mechanism of the cell to minimize the harmful effects of free radicals. The fact that uranyl acetate increases MDA levels and induces antioxidant enzyme activities can be explained by triggering oxidative stress. The decrease observed in MDA, SOD and CAT levels in Group V and Group VI treated with sage+uranyl acetate shows that sage provides protection against the biochemical toxicity of uranyl acetate. This healing property is closely related to the antioxidant, antiradical and metal chelating activities of sage.

The effects of uranyl acetate and sage application on the root anatomy of A. cepa are shown in Fig.6 and Table 3. No damage was observed in the root meristem cells of Group II and Group III, which were exposed to two different doses of sage with the control group. In Group IV exposed to uranyl acetate at a dose of 0.1mg/mL, epidermis and cortex cell damage, as well as meristematic cell damage in the form of flattened cell nucleus were observed. Co-administration of sage with uranyl acetate caused reductions/improvements in the severity of observed meristematic cell damage by reducing the negative effects of uranyl acetate, depending on the dose. It was determined that this decrease in the severity level was more pronounced at 380mg/L dose of sage.

Meristematic cell damages induced by uranyl acetate. Normal appearance of epidermis cells (a), normal appearance of cortex cells (b), normal appearance of cell nucleus-oval (c), epidermis cell damage (d), cortex cell damage (e), flattened cell nucleus (f).

Although there is no study in the literature that deals with the anatomical changes caused by uranium or uranyl acetate exposure in plant root tip meristematic cells, there are some studies on the anatomical effects of other heavy metals. Grel et al.34 reported that 2.4, 8.0 and 12.5mg/L Cr doses caused anatomical damage in the form of cell deformation, thickening of the cortex cell wall, flattened cell nucleus and necrosis in root tip meristematic cells of A. cepa. They also stated that the severity of these damages was dose dependent. avuolu et al.43 observed anatomical damage such as cell deformation, necrosis, flattening cell nucleus, thickening of the cortex cell wall, inclearly vascular tissue and accumulation of some substances in cortex cells in A. cepa root tip meristematic cells exposed to Hg at 25, 50 and 100mg/L doses. Girasun et al.35 detected cell damage such as thickening of the cortex cell wall, cell deformation, inclearly vascular tissue and necrosis in A. cepa root tip meristem cells of 50, 100 and 200mg/L doses of Pb exposure, the severity of which increased with the application dose. Macar et al.36 reported that 5.5mg Co dose promoted damages such as epidermis cell deformation, thickening of the cortex cell wall and flattened cell nucleus in A. cepa root tip meristematic cells.

This suggests that this epidermis and cortex cell damage induced by uranium occurs as a result of the defense mechanisms developed by plants against heavy metal ions. Because the roots have increased the number and frequency of the epidermis and cortex cells in order to prevent uranium from entering the cell, and these damages may have occurred as a result of the compression/suppression of the cells. The information in the literature that plants develop different defense mechanisms against heavy metal toxicity, such as accumulation, storage and crystallization of metals in certain regions, or changes in the cell membrane and cell wall, increase in vacuole numbers and metal-binding protein synthesis44, supports our this idea.

In recent studies, different plant extracts such as lycopene, carotene, Ginkgo biloba L., green coffee, green tea and stinging nettle are used to reduce toxicity promoted by toxic agents such as heavy metal ions. In this study, sage treatment provided significant protection against the physiological, biochemical, cytogenetic and anatomical abnormalities exhibited by the application of uranyl acetate in the A. cepa root tip cells. It provided improvement in germination-related parameters such as root length and weight gain, and decreased MN and CAs frequencies, which were detected at high rates after uranyl acetate application. These improvements increased depending on the dose and the highest protection was obtained at the dose of 380mg/L. In this study, it was determined that sage has antiradical property and scavenges the DPPH radical at a rate of 72.9%. Sage is a powerful antioxidant compound, which also exhibits an important metal chelating activity. These powerful properties of sage are related to the active ingredients it contains. The greatest role in the protective role of sage is the antioxidant activity exhibited due to phenolic compounds such as carnosic acid, carnosol, rosmarinic acid and camphor in the content. There are some studies in the literature focused on the antioxidant role of sage. For example, Lima et al.45 investigated the antioxidant potential of traditional water infusion (tea) of sage in vivo in mice and rats. In conclusion, it was determined that replacing the water in the diet of rodents with sage for 14days did not affect the body weight and food consumption of the animals. They also reported that sage did not cause liver toxicity, liver GST activity was increased in rats (24% rate) and mice (10% rate) drinking sage, on the other hand, sage caused an improvement in the antioxidant status of hepatocytes, increased GSH levels and provided a protection against lipid peroxidation. Horvthov et al.46 investigated the protective effect of sage extract against oxidative stress to which liver cells of SpragueDawley rats are exposed. As a result, no negative effects were observed on basal DNA damage levels and SOD activities in hepatocyte cells of animals that drank sage for 14days, and no changes were detected in the biochemical parameters of blood plasma. On the contrary, they determined that sage extract significantly increased GPx activity, decreased DNA damage levels caused by oxidants, and provided antioxidant protection by increasing GSH levels. Alshubaily and Jambi47 investigated the possible protective role and antioxidant activity of sage extract against metabolic disorders caused by hypercholesterolemic diet in heart and testicular tissues of rats. In conclusion, they determined that the hypercholesterolemic diet significantly increased serum lipid content, cardiac marker enzyme activities, MDA levels, and significantly decreased high-density lipoprotein-cholesterol levels in testes and heart tissues. They observed that the co-administration of hypercholesterolemic diet and sage extract reduced the damage caused by the hypercholesterolemic diet by causing a decrease in lipid peroxidation, induction of heart and testis functions, and increased activity. They reported that essential oil, phenolic contents and other antioxidant components contained in sage extract were effective in this.

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Metal chelating and anti-radical activity of Salvia officinalis in the ameliorative effects against uranium toxicity | Scientific Reports - Nature.com

(Photo : Dr. Yesu Addepalli)

In addition to studying the complex chemical and physical properties of living things, dissecting their cellular structures, and understanding how they interact with different compounds, biochemists play a key role in providing the foundational knowledge and science used to develop health treatments and medical drugs.

Dr. Yesu Addepalli is a renowned expert in the field of biochemistry, having played a critical role in the drug discovery and synthesis of biologically active small molecules. This work has the potential to be revolutionary for the biopharmaceutical industry, as our society battles a wide variety of viruses and diseases. The PHD holder has a unique and valuable perspective thanks to his multifaceted education in organic chemistry, medicinal chemistry, and chemical biology.

Dr. Addepalli was instrumental in the development of antiparasitic drugs for leishmaniasis and trypanosomiasis. When asked about his methods, he explains: "My efforts were geared towards the utilization of chemical derivatization and forward genetic approaches to study a class of compounds that selectively test derivatives for selective activity on Leishmania tubulin and trypanosomatids. [From there, I] assessed their stability, solubility, cell permeability, and in vivo PK properties. [I] performed proof-of-concept testing in the mouse model of leishmaniasis and used a modular synthetic strategy, and Cryo-EM techniques to discover the binding site of a class of pyrimidinone derivatives. [Finally I] optimized promising agents for oral administration and performed dose response testing in animal models."

This work, at the University of Texas Southwestern Medical Center's Ready laboratory, will allow the development of compounds with a high therapeutic index for the treatment of trypanosomatid infections, based on the identification of molecules that inhibit targeting parasite tubulin polymerization. The newly found understanding of the drug target and mechanism brings promise for the treatment of these arthropod-borne diseases.

Dr. Yesu Addepalli earned his Master of Science degree in organic chemistry from the Government College (Autonomous), Rajahmundry in India before going on to complete his doctoral degree in organic chemistry under the guidance of Research Advisor Prof. Yun He at Chongqing University in China. Most recently, he has been working in a postdoctoral position with esteemed-researcher Professor Joseph Ready at the University of Texas Southwestern Medical Center, which provides him with both the tools and community to evolve and deepen his studies.

"I find bioactive small molecules to be fascinating. The design, synthesis, purification, and characterization of viruses and [their] treatment drugs are a wonder to behold, study, and develop." Dr. Addepalli shares, "Some people find beauty in the world around [them], but I see beauty in the microscopic world of viruses and find great pleasure in being instrumental in halting the spread of viruses through synthesizing biopharmaceuticals."

Although the work is rewarding,Dr. Yesu Addepalli recognizes that it is also a great responsibility, as each challenge is fundamentally a battle between life and death. He is grateful for the diversity of knowledge and skills that his team holds, as it brings them closer to streamlined bioactive molecule development. He is also currently collaborating with biologists at UT Southwestern, and elsewhere, using high-throughput screening strategies to discover small molecules with promising biological activity in an effort to identify compounds and molecules that will push the boundaries of genetic studies. The characterization of biologically active small molecules is a breakthrough for the development of novel therapeutics for neurodegenerative and infectious diseases, as well as for cancer.

Dr. Addepalli's esteemed work has been featured in a variety of reputable publications, and he also has a US patent for his team's work specifically with novel antiparasitic compounds and methods. He is an active member of the American Society for Biochemistry and Molecular Biology, as well as the Society for Immunotherapy of Cancer. In his free time, he also enjoys reviewing for publications such as Tetrahedron and Heterocyclic Chemistry.

His work revolves around molecules and compounds that are far too small to see with the naked eye, but the impact of his work has a very large scope. As our society has recently been reminded of the threat that these microscopic elements can bring, the work of Dr. Addepalli is perhaps more important than ever before. Gaining a stronger understanding of how these microscopic molecules create disease will help us to understand how to reverse and treat the disease. As they say, knowledge is power.

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Expert In Biochemistry Dr. Yesu Addepalli Works On A Micro Level To Bring Macro Changes To The Development Of Novel Therapeutics - Tech Times

Home / News & Events / Be Open To A Lot of Things: A Brandeis Alums Advice on the Biochemistry & Biophysics Program

August 22, 2022

Sydney Adams | Graduate School of Arts and Sciences

Prior to receiving her PhD in Biochemistry & Biophysics from Brandeis, Karina Herlambang PhD22 studied biochemistry at the University of Wisconsin-Madison, where she worked for Brandeis alumnus Michael Cox PhD79 studying DNA repair mechanisms as a research assistant. She explains, I was still not sure what biochemistry was really all about, but, as time went on, my fascination towards all these proteins that made up who we are as a living organism only grew stronger. I knew that I wanted to spend more time doing research, so I decided to pursue a PhD. Cox spoke nothing but great things about Brandeis, and after speaking with other alums at UW Madison, Brandeis immediately became one of her top choices. She says Brandeis collaborative environment and top quality research along with our, close proximity to Boston, which is the biotech hub in the country helped to finalize her decision.

Herlambang says, The Brandeis community is just really wonderful! Everyone is willing to go above and beyond to help each other out. She went on to say, Every interaction that I had with the faculty at Brandeis has been really positive. She singled out Professor Jeff Gelles for particular praise, for playing a major role in my scientific and personal development. She partially credits her experience to the typically small class size at Brandeis which allowed her to get to know everyone pretty well. Her favorite part of the PhD program was the ability to collaborate with other lab groups from different departmentsnot just within Brandeis but also in other institutions. That really helped me to get helpful input and learn other techniques that otherwise I would not have been exposed to.

Herlambang made use of another Brandeis resource to secure her current role at Intellia Therapeutics. Working with the Professional Development team enabled her to receive crucial feedback on my resume and ask for interview tips. She also says that the Professional Development team initiated connections with Brandeis alums that currently work in some of the companies that I was applying for. Thats how I ended up applying to Intellia Therapeutics, she says. Little did I know, one of my interviewers was actually an alum of my lab, so that made the interview less intimidating.

While Herlambang cant share any of the projects she is currently working on at Intellia Therapeutics as a scientist in the RNA technologies group, she credits her time at Brandeis for helping her prepare for her role. Her work focuses on improving mRNA stability to enhance our gene editing platform. Herlambang says the scientific community at Brandeis challenged me to think critically and allowed me to be exposed to different areas of research. She went on to say that her experience at Brandeis, made me realize how important collaboration is and interdisciplinary research is even more evident in industry.

As for advice for students interested in pursuing a degree from Brandeis Biochemistry & Biophysics program, Herlambang says, Be open to a lot of things and start networking early. Exposing yourself to different areas of research or career path right from the beginning should help you figure out what you really want to do afterward. Being a Brandeisian itself is already a huge advantage. You might not be aware of this but you have this large network like the Brandeis alumni connection that you should take advantage of. It might be intimidating at first to reach out, but most people are willing to help.

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Be Open To A Lot of Things: A Brandeis Alum's Advice on the Biochemistry & Biophysics Program - brandeis.edu