RECENT EVALUATIONS



Evaluations of the following applications to Vetenskaprådet (Swedish Research Council) are shown below:

VR Medicine  2015-2018


VR Natural Sciences 2010-2014






VR Medicine  2015-2018

Below is original VR document with evaluation of the application. Readers are directed to the scanned original VR-document by clicking here (document size 2 Mb).


2014-2997

Chattopadhyaya, Jyoti

Uppsala universitet

lnstitutionen for cell- och molekylarbiologi

Kemisk Biologi

Project Research Grant

 

Project title
New Nucleolytically Stable Antisense/siRNA!miRNA Oligonucleotides For The Target mRNA
Degradation

 
Research area
                          Evgroup

*Ovrigt generellt                         Basic disease mechanisms: Molecular, cellular and aspects (Mf:I-E3),

 

 

Novelty and originality                                6

(1 =Poor, 2=Weak, 3=Good, 4=Very good, 5=Very good to excellent, 6=Excellent, ?=Outstanding)

 

The project deals with chemically modified nucleic acids (carba-LNAs) with favorable properties. More specific, using different test scenarios (HIV, COPD, infection/inflammation), the problem of delivery of RNAi-based agents to target cells shall be addressed now. This project has excellent novelty and originality as it addresses a very important and actual problem for future therapies. Yet, is has to be considered that this is intensely investigated worldwide and some groups and companies might be relatively close to solutions.

 

Scientific quality of the project          5

(1 =Poor, 2=Weak, 3=Good, 4=Very good, 5=Very good to excellent, 6=Excellent, ?=Outstanding)

 

The research plan is in principle very good to excellent. Yet, the description is partly difficult to access as it contains substantial insertions of lengthy citations, which would better have been inserted as numbers, many long listings, and is redundant on several occasions. More clarity and details instead of repetitions would have been favorable. There are also some drawbacks in the research  plan. it is acknowledged that linking fluorescent probes is desirable for visualization purposes. But adding such groups will  likely modulate the properties of the nucleic acid molecules, so that it remains an open question, whether this will  reveal the true localization/destination of the nucleic acids. The most appropriate readout is probably knockdown efficacy as silencing only would take place in case of reaching the correct final destination (e.g. RISC). One may note that the HIV genome is pretty small and well investigated, so that it is questionable, in how far a genome-wide scan in the HIV sequence can provide information about novel targets.  Or is it meant to find new regions in the viral genome that may show better accessibility for nucleic acid-based therapeutics?

 

On the positive side is the fact that the applicant clearly has a focus on developing ways of tissue specific distribution, aiming to target real human disease types.



Merits of the applicant(s)
                      6

(1 =Poor, 2=Weak, 3=Good, 4=Very good, 5=Very good to excellent, 6=Excellent, ?=Outstanding)

 

Taken together, the two applicants have an excellent track record in the field with a high quantity of publications, including also numerous high quality publications and some patents relevant for the field. The main applicant has a long-standing experience in the core endeavor, operating at competitive level also in an international context.

 


Feasibilit
y                                                          3

(
1 =Not feasible, 2=Partly feasible, 3=Feasible)

 

The research plan is very broad and would profit from more focus. However, the applicant actually documents impressive progress and improvements that are elicited by the carba-LNA modification with regard to stability, selectivity and efficacy. This provides good support that the approach is feasible.

 

Previous results for continuation projects (only to be assessed tor applications containing Appendix D  "Scientific report")

 

 


Overall grade for the application's scientific
...       6

(1 =Poor, 2=Weak, 3=Good, 4=Very good, 5=Very good to excellent, 6=Excellent, ?=Outstanding)

 

Motivation for the overall assessment of the application's scientific quality

The proposal addresses an exciting area and a prevalent problem, so that it bears excellent high novelty and originality. The research plan in principle is straight forward, but is a bit too broad, has some deficits, and ultimately is not formulated very well compared to what would be considered as basic standard. However, the expertise, track records and the fact that systematic and continuous research of the applicant has led to this point, where therapeutic applications become clearly visible provides substantial confidence in feasibility and potential success. In  conclusion, the overall quality of the application is excellent.

 

 

 

Collected Evaluations MH-F3, 2014-2997 Chattopadhyaya, Jyoti






VR Natural Sciences 2010-2014


Below is an English translation of the original VR document. Readers are directed to original VR-document in Swedish by clicking here (document size 2 Mb).

Dnr 2010-4991

 

Surname, Name: Chattopadhyaya, Jyoti, Uppsala University,
Department of Cell- and Molecular Biology, Bioorganic Chemistry

Grant: Project grant

 

Project title: Synthesis, Structure & Function of RNA

 

 

Research field/Subject area: Biochemistry and biotechnology

Panel: Organic Chemistry, Inorganic chemistry and material chemistry (NT-D2)


GROUP’s RATING:                                                                       5
1-5 (1=Inadequate, 2=Good, 3=Very good, 4=Excellent, 5=World’s leading)

Research field for rating 4 (excellent) and 5 (world’s leading):
Bioorganic Chemistry
OVERALL RATING:                                                                     
5
1-5 (1=rejection, 2=low, 3=medium, 4=high, 5=highest)

 

The applicant’s competence:

Jyoti Chattopadhyaya is employed as Professor at Uppsala University since 1985. He has supervised 30 Ph.D. students from start to the disputation. Chattopadhyaya’s RNA-research is holding very high international level. He is well-published with a large number of publications in prestigious scientific journals and his works are well-cited by others.

Project’s quality:

Chattopadhyaya’s project plan, which with large margins exceeds 10 pages stipulated in instructions, describes three main goals, all coupled to RNA: 1) specific RNA-synthesis, 2) structure and conformational determination of RNA and 3) studies of RNA function. All issues are coupled with each other. Within synthesis part of the project new methods of RNA synthesis are going to be studied including development of new protection groups strategy, conducting and improving methods of synthesis for production of isotope labeled oligo-RNA (20-80 mer) in large-scale using solid state synthesis technique as well as to produce various types of both cyclic and branched RNA derivatives for further studies.  Chattopadhyaya describes very evtensive plan for both conformational studies and for studies of functions of various RNA-systems. These investigations are going to be performed mostly with help of different NMR-methods. The number of approaches to reach these goals mentioned in the plan is high which however can be motivated with the problems being both important and very interesting. The project consistently aims to highlight  and to try to explain how the structure of RNA is influencing its function. For example he plans to study various catalytical RNA cleavage process and thereby obtaining knowledge which may lead to possibility to develop synthetic nucleases. Furthermore it presents an opportunity to develop novel antibiotics against resistant bacteria by targeting ribosomal RNA, to study and here different modeling studies are going to be implemented.  The intended study targets within the projects are both original and of high relevance.

Project’s feasibility:

Probability that Chattopadhyaya’s proposed project will be successful is very high and the project is feasible. The last mentioned “antibiotics”-project should however be marked as really high-risk project but if it is succeeded it can lead to great and important consequences.

 

Panel opinion NT-D2, 2010-4991 Chattopadhyaya, Jyoti